@article {pmid30651539, year = {2019}, author = {Mondal, M and Bertranpetit, J and Lao, O}, title = {Approximate Bayesian computation with deep learning supports a third archaic introgression in Asia and Oceania.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {246}, doi = {10.1038/s41467-018-08089-7}, pmid = {30651539}, issn = {2041-1723}, abstract = {Since anatomically modern humans dispersed Out of Africa, the evolutionary history of Eurasian populations has been marked by introgressions from presently extinct hominins. Some of these introgressions have been identified using sequenced ancient genomes (Neanderthal and Denisova). Other introgressions have been proposed for still unidentified groups using the genetic diversity present in current human populations. We built a demographic model based on deep learning in an Approximate Bayesian Computation framework to infer the evolutionary history of Eurasian populations including past introgression events in Out of Africa populations fitting the current genetic evidence. In addition to the reported Neanderthal and Denisovan introgressions, our results support a third introgression in all Asian and Oceanian populations from an archaic population. This population is either related to the Neanderthal-Denisova clade or diverged early from the Denisova lineage. We propose the use of deep learning methods for clarifying situations with high complexity in evolutionary genomics.}, }
@article {pmid30615384, year = {2017}, author = {Kulyutsina, ER and Tatarchenko, IP and Levashova, OA and Denisova, AG and Drujinina, TA}, title = {[The interrelationship of indices of hemocysteine and genetic polymorphisms conditioning disorders of folates metabolism in healthy population].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {62}, number = {2}, pages = {82-87}, pmid = {30615384}, issn = {0869-2084}, abstract = {The study was carried out to investigate relationship of the level of homocysteine and genetic polymorphisms conditioning disorders of metabolism of folates in healthy population and of various age and gender groups. The study covered 168 donors: 98 males and 70 females. Two gender groups were singled out and in each of them age groups: 18-31, 32-45 and 46-60 years old. The analysis of concentration of homocysteine was implemented using immune chemiluminescence analysis. The polymerase chain reaction was applied for analyzing genetic polymorphisms associated with disorders of folate cycle by genes MTHFR (met hylentetrahydrofolatereductase) (polymorphisms MTHFR: 677 C>T and MTHFR: 1298 A>C), MTR (B12-dependent methionine-synthetase) (polymorphism MTR: 2756 A>G) and MTRR (methionine-synthetase-reductase) (polymorphism MTRR: 66 A>G). The level of homocysteine in blood of donors was reliably higher in male groups of 18-31 and 32-45 years old as against female groups comparable by age. The study established higher rate of occurrence of heterozygous genotypes bringing unfavorable types of polymorphisms of MTHFR and MTRR genes both in male and female groups. The study established higher rate of occurrence of unfavorable genotypes in examined patients in comparison with publications' data. The established statistically significant inverse correlation of concentration of homocysteine and genetic polymorphisms associated with disorders of folate cycle in individuals of young and middle age mainly males, permits to draw a conclusion about absence of their direct relationship. Therefore, implementation of genetic liability to increasing of homocysteine can occur under effect of external unfavorable factors.}, }
@article {pmid30592826, year = {2016}, author = {Bulavin, VV and Chaplyuk, AL and Kal'manov, AS and Solomka, AV and Denisova, MP and Blinov, VV}, title = {[Modern methods of diagnosis of chronic viral hepatitis used in the practice of the military-medical examination].}, journal = {Voenno-meditsinskii zhurnal}, volume = {337}, number = {9}, pages = {10-17}, pmid = {30592826}, issn = {0026-9050}, abstract = {Modern methods of diagnosis of chronic viral hepatitis used in the practice of the military-medical examination. The article presents current views on the classification of chronic viral hepatitis. The characteristic of methodical diagnostic approaches is presented: The attention to the etiological pathology verification is paid. The results of study on clinical characteristics of patients with chronic viral hepatitis are used as the basis for the developed criteria for evaluating fitness for military service.}, }
@article {pmid30592887, year = {2018}, author = {Kirpichenkova, EV and Korolev, AA and Onishchenko, GG and Nikitenko, EI and Lipatov, DV and Kuz'min, AG and Dyskin, YA and Denisova, EL and Fetisov, RN}, title = {[Study of lutein and zeaxanthin content in the diet with the assessment of the relationship between the level of alimentary intake of non-vitamin carotenoids and the density of the macular region of the retina at a young age].}, journal = {Voprosy pitaniia}, volume = {87}, number = {5}, pages = {20-26}, doi = {10.24411/0042-8833-2018-10049}, pmid = {30592887}, issn = {0042-8833}, abstract = {Lutein and zeaxanthin are carotenoid pigments that affect the function of the visual analyzer. They selectively accumulate in the yellow spot of the retina, form macular pigment and determine the density of the retina macula. Lutein and zeaxanthin slow down the progression of age-related macular degeneration, a leading cause of senior-age blindness. The main food sources of non-vitamin carotenoids are green leafy vegetables, zucchini, pumpkin, green peas, broccoli. The aim of the study is a retrospective assessment of the levels and sources of alimentary intake of lutein and zeaxanthin in young people and research of the effect of lutein and zeaxanthin in the diet on macula density. A specially designed questionnaire was used to quantify the content of lutein and zeaxanthin in the diet, reflecting the amount of consumption of the main sources of these carotenoids on the day preceding the survey. A non-invasive non-contact method of optical coherence tomography of the retina was used to determine the density of the macula. The study involved 96 students of Sechenov University at the age of 21-27 years. The study found that only 6.25% of the respondents had daily intake of lutein and zeaxanthin of 6 mg or more, 8.33% had 4.6-5.9 mg, 8.33% had 3.0-4.5 mg, in 18.75% - 1.5-2.9 mg, in 45.83% <1.4 mg. 12.5% of respondents didn't include sources of lutein and zeaxanthin in the diet. The more common sources of lutein and zeaxanthin in the diet were eggs and fresh tomatoes. Retinal density indices corresponded to the age standards in the majority of the examined. In 8.3% surveyed the thickness of the retina was decreased, and 4.2% had higher thickness of the retina in comparison with the standards. Significant differences in the Central subfield thickness in men and women were revealed. There was no dependence of the levels of lutein and zeaxanthin coming from food sources on the retina thickness indicators.}, }
@article {pmid30592878, year = {2018}, author = {Martinchik, AN and Baeva, VS and Peskova, EV and Kudryavtseva, KV and Denisova, NN and Lavrinenko, SV and Kambarov, AO and Badtieva, VA and Nikityuk, DB}, title = {[Actual liquid consumption by highly qualified athletes in the mode of the training process].}, journal = {Voprosy pitaniia}, volume = {87}, number = {3}, pages = {36-44}, doi = {10.24411/0042-8833-2018-10029}, pmid = {30592878}, issn = {0042-8833}, abstract = {The purpose of the study was to evaluate the actual intake of fluids by athletes of various sports during the day with one and two training sessions before, during and after workout. The dietary intake, including consumption of various types of liquid foods and beverages, was evaluated by the method of 24-hour recall in 280 athletes of high qualification (candidates for masters and masters of sports) of both gender of various sports during the training period. It has been established that the main drink of rehydration was drinking bottled water. Bottled water was consumed on average by 86% of athletes. It was consumed by 95-96% of sportsmen from the group of single combats and power kinds, whereas in other groups the share of water consumers was less - 67-79%. In second place in terms of percentage of consuming was tea. Consumption of sports drinks was observed only during training by athletes from the group of cyclic sports (31%) and single combat (11%). Calculating the per capita fluid intake of athletes who had 2 workouts a day showed that athletes from the martial arts group consumed the largest volumes of fluid in the mode of both training sessions as compared to representatives of other sports. Athletes of other sports consumed on average less liquid in the 2nd training mode compared to the 1st one. The total fluid intake during two training sessions was maximum in the group of martial arts and was minimum in the group of complex coordination sports. It should be specially noted a small proportion of athletes who consumed specialized sports drinks - only 17% of athletes and more than half of them - cyclical sportsmen. Consumption of liquid food outside training has been observed in 76% of athletes. The mean volume of consumed liquid products varied by the user from 382 and 437 ml in complex coordination and game sports up to 504-553 ml in other sports. The daily fluid intake was maximum (2326 ml) in athletes engaged in martial arts, minimum (1009 ml) - in athletes of complex coordination sports.}, }
@article {pmid30566634, year = {2018}, author = {Reher, D and Key, FM and Andrés, AM and Kelso, J}, title = {Immune gene diversity in archaic and present-day humans.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evy271}, pmid = {30566634}, issn = {1759-6653}, abstract = {Genome-wide analyses of two Neandertals and a Denisovan have shown that these archaic humans had lower genetic heterozygosity than present-day people. A similar reduction in genetic diversity of protein-coding genes (gene diversity) was found in exome sequences of three Neandertals. Reduced gene diversity, and particularly in genes involved in immunity, may have important functional consequences. In fact, it has been suggested that reduced diversity in immune genes may have contributed to Neandertal extinction. We therefore explored gene diversity in different human groups and at different time points on the Neandertal lineage with a particular focus on the diversity of genes involved in innate immunity and genes of the Major Histocompatibility Complex (MHC).We find that the two Neandertals and the Denisovan have similar gene diversity, both significantly lower than any present-day human. This is true across gene categories, with no gene set showing an excess decrease in diversity compared to the genome-wide average. Innate immune-related genes show a similar reduction in diversity to other genes, both in present-day and archaic humans. There is also no observable decrease in gene diversity over time in Neandertals, suggesting that there may have been no ongoing reduction in gene diversity in later Neandertals, although this needs confirmation with a larger sample size. In both archaic and present-day humans, genes with the highest levels of diversity are enriched for MHC-related functions. In fact, in archaic humans the MHC genes show evidence of having retained more diversity than genes involved only in the innate immune system.}, }
@article {pmid30552618, year = {2018}, author = {Starshinova, A and Zinchenko, Y and Filatov, M and Denisova, N and Istomina, E and Landa, S and Burdakov, V and Churilov, L and Sapozhnikova, N and Pavlova, M and Stepanenko, T and Mayevskaya, V and Yablonskiy, P}, title = {Specific features of immune complexes in patients with sarcoidosis and pulmonary tuberculosis.}, journal = {Immunologic research}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12026-018-9052-1}, pmid = {30552618}, issn = {1559-0755}, abstract = {Clinical and radiological features of tuberculosis and sarcoidosis are quite overlapping, and therefore, a diagnostic dilemma often persists. There are no commonly accepted criteria for the diagnosis of sarcoidosis due to the lack of data on the etiology of the disease. The exclusion of tuberculosis in every patient with suspected sarcoidosis is a mandatory stage of diagnosis, especially in countries with a high burden of tuberculosis. A prospective study was conducted with two groups of patients: group I (n = 50)-patients with pulmonary sarcoidosis established according to standard criteria; group II (n = 28)-patients with pulmonary tuberculosis with bacterial excretion. The control group (n = 24) was presented by healthy subjects. The examination complex included x-ray, bacteriological, immunological (Mantoux test with 2 TE, TB.SPOT test), and histological methods. All patients and healthy subjects were assessed for immune complexes with the use of the dynamic light scattering (DLS) method and adding of "healthy lung tissue extract" antigens and specific tuberculosis antigens ESAT-6 and SFP-10 in vitro. Significant differences were found in determining specific immune complexes in patients with pulmonary sarcoidosis and pulmonary tuberculosis. Registration of specific immune complex formation with "healthy lung tissue extract" in 100% cases may indicate the autoimmune nature of sarcoidosis. The absence of the immune complex formation in response to ESAT-6/SFP-10 antigens can be used for the differential diagnosis of two diseases. The diagnostic significance of the DLS method was 100% for sarcoidosis and 92.2% for tuberculosis. The data obtained in the study allows not only understanding the etiology of sarcoidosis, but also obtaining new criteria for the differential diagnosis of tuberculosis and pulmonary sarcoidosis.}, }
@article {pmid30546947, year = {2019}, author = {Pol, JG and Acuna, SA and Yadollahi, B and Tang, N and Stephenson, KB and Atherton, MJ and Hanwell, D and El-Warrak, A and Goldstein, A and Moloo, B and Turner, PV and Lopez, R and LaFrance, S and Evelegh, C and Denisova, G and Parsons, R and Millar, J and Stoll, G and Martin, CG and Pomoransky, J and Breitbach, CJ and Bramson, JL and Bell, JC and Wan, Y and Stojdl, DF and Lichty, BD and McCart, JA}, title = {Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials.}, journal = {Oncoimmunology}, volume = {8}, number = {1}, pages = {e1512329}, doi = {10.1080/2162402X.2018.1512329}, pmid = {30546947}, issn = {2162-4011}, abstract = {Multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. We evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (NHP) (Macaca fascicularis). Primates received a replication-deficient adenoviral prime, boosted by the oncolytic Maraba MG1 rhabdovirus. Both vectors expressed the human MAGE-A3. No severe adverse events were observed. Boosting with MG1-MAGEA3 induced an expansion of hMAGE-A3-specific CD4+ and CD8+ T-cells with the latter peaking at remarkable levels and persisting for several months. T-cells reacting against epitopes fully conserved between simian and human MAGE-A3 were identified. Humoral immunity was demonstrated by the detection of circulating MAGE-A3 antibodies. These preclinical data establish the capacity for the Ad:MG1 vaccination to engage multiple effector immune cell populations without causing significant toxicity in outbred NHPs. Clinical investigations utilizing this program for the treatment of MAGE-A3-positive solid malignancies are underway (NCT02285816, NCT02879760).}, }
@article {pmid30538215, year = {2018}, author = {Denisova, TG and Gerasimova, LI and Pakhmutova, NL and Mahesh, S and Vithoulkas, G}, title = {Individualized Homeopathic Therapy in a Case of Obesity, Dysfunctional Uterine Bleeding, and Autonomic Dystonia.}, journal = {The American journal of case reports}, volume = {19}, number = {}, pages = {1474-1479}, doi = {10.12659/AJCR.913328}, pmid = {30538215}, issn = {1941-5923}, abstract = {BACKGROUND Obesity is one of the leading causes of morbidity and mortality globally and challenging to treat because of the multifactorial etiology and presentation. Individualized homeopathy takes into account factors that led to a patient's health condition and hence may have a role in the treatment of obesity and related co-morbidities; co-morbidities that may arising from the same etiology may respond as a whole to homeopathy treatment. CASE REPORT A 39-year-old Russian female who developed multiple problems after severe emotional stress was treated with individualized classical homeopathic therapy. Obesity, dysfunctional uterine bleeding, and dysautonomia were pathologies that showed improvement. CONCLUSIONS The response in this patient's case, supports the need for further investigation on the relevance of individualized homeopathy in these related conditions.}, }
@article {pmid30450552, year = {2018}, author = {Safronova, EI and Dydykin, SS and Grigorevskiy, ED and Tverye, EA and Kolchenko, SI and Piskunova, NN and Denisova, AV and Titova, GP and Parshin, VD and Romanova, OA and Panteleyev, AA}, title = {Experimental animal model for assessment of tracheal epithelium regeneration.}, journal = {The Laryngoscope}, volume = {}, number = {}, pages = {}, doi = {10.1002/lary.27480}, pmid = {30450552}, issn = {1531-4995}, support = {1386//National Research Center Kurchatov Institute/ ; }, abstract = {OBJECTIVES/HYPOTHESIS: To develop an experimental model in rabbits for assessment of tracheal epithelium regeneration through application of either natural or artificial polymer scaffolds.

STUDY DESIGN: First, we identified the size of full-thickness mucosal defect, which does not allow self-healing (a "critical defect"), thus representing an adequate experimental model for regenerative therapy of tracheal epithelium damage. Then, two methods of polymer scaffold fixation at the site of the epithelium defect were compared: suturing and fixation with a stent. This was done through: 1) formation of a full-thickness anterolateral mucosal defect by tracheal mucosa excision; and 2) fixation of the scaffold at the site of the tracheal epithelium defect using sutures (through a tracheal wall "window") or a vascular stent (through a small tracheal incision).

RESULTS: The dimension of a critical anterolateral mucosal defect of the trachea for rabbits was found to be 1.5 cm in length and more than 50% of the tracheal circumference. Fixation of the scaffold with a stent proved to be more efficient due to a uniform distribution of the pressure over the entire surface of the scaffold, whereas the suturing of the scaffold provided unsatisfactory results. In addition, fixation of the scaffold by suturing required formation of a large "window" in the tracheal wall. Thus, using the stent appeared to be technically less complicated and much less traumatic as compared to suturing.

CONCLUSION: We present an experimental in vivo animal model of tracheal epithelium injury and recovery. It can be effectively used with certain further modifications as a basis for routine testing of bioengineered constructs.

MATERIALS AND METHODS: We enrolled in the study 163 male patients admitted to the coronary unit for acute coronary syndrome (ACS) and 38 male practically healthy volunteers (PHV). ADP induced blood-clotting time (ADP BCT) was measured as time (sec) between addition of ADP (10 μcmol) to recalcificated sample of citrate blood and clot formation. In healthy volunteers ADP BCT was determined before and 45 minutes after oral administration of acetylsalicylic acid (ASA, 250 mg). Risk of cardiovascular death was calculated using the GRACE score. Platelet function tests were performed by optical aggregometry. Follow-up period for patients with ACS was 24 months. The primary end point (PEP) was the composite of cardiovascular death and rehospitalization.

RESULTS: In ACS patients ADP BCT was significantly lower than in PHV: 134.8 (109.9; 161.3) vs 85.7 (60.5; 108.7) sec, p=0.015. In PHV ASA increased ADP BCT - 103.2 (95.1; 130.7) vs 133.1 (102.8; 154.3) sec, p=0.041. ADP BCT correlated with age in both PHV and patients (R= -0.431, p.}, }
@article {pmid30289977, year = {2018}, author = {Johannessen, TA and Hasan-Olive, MAM and Zhu, H and Denisova, O and Grudic, A and Latif, M and Saed, H and Varughese, JK and Røsland, GV and Yang, N and Sundstrøm, T and Nordal, A and Tronstad, KJ and Wang, J and Lund-Johansen, M and Simonsen, A and Janji, B and Westermarck, J and Bjerkvig, R and Prestegarden, L}, title = {Thioridazine inhibits autophagy and sensitizes glioblastoma cells to temozolomide.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.31912}, pmid = {30289977}, issn = {1097-0215}, abstract = {Glioblastoma multiforme (GBM) has a poor prognosis with an overall survival of 14-15 months following surgery, radiation and chemotherapy using temozolomide (TMZ). A major problem is that the tumors acquire resistance to therapy. In an effort to improve the therapeutic efficacy of TMZ, we performed a genome-wide RNA interference (RNAi) synthetic lethality screen to establish a functional gene signature for TMZ sensitivity in human GBM cells. We then queried the Connectivity Map database to search for drugs that would induce corresponding changes in gene expression. By this approach we identified several potential pharmacological sensitizers to TMZ, where the most potent drug was the established antipsychotic agent Thioridazine, which significantly improved TMZ sensitivity while not demonstrating any significant toxicity alone. Mechanistically, we show that the specific chemosensitizing effect of Thioridazine is mediated by impairing autophagy, thereby preventing adaptive metabolic alterations associated with TMZ resistance. Moreover, we demonstrate that Thioridazine inhibits late-stage autophagy by impairing fusion between autophagosomes and lysosomes. Finally, Thioridazine in combination with TMZ significantly inhibits brain tumor growth in vivo, demonstrating the potential clinical benefits of compounds targeting the autophagy-lysosome pathway. Our study emphasizes the feasibility of exploiting drug repurposing for the design of novel therapeutic strategies for GBM. This article is protected by copyright. All rights reserved.}, }
@article {pmid30278065, year = {2018}, author = {Hoover, KC}, title = {Intragenus (Homo) variation in a chemokine receptor gene (CCR5).}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0204989}, doi = {10.1371/journal.pone.0204989}, pmid = {30278065}, issn = {1932-6203}, abstract = {Humans have a comparatively higher rate of more polymorphisms in regulatory regions of the primate CCR5 gene, an immune system gene with both general and specific functions. This has been interpreted as allowing flexibility and diversity of gene expression in response to varying disease loads. A broad expression repertoire is useful to humans-the only globally distributed primate-due to our unique adaptive pattern that increased pathogen exposure and disease loads (e.g., sedentism, subsistence practices). The main objective of the study was to determine if the previously observed human pattern of increased variation extended to other members of our genus, Homo. The data for this study are mined from the published genomes of extinct hominins (four Neandertals and two Denisovans), an ancient human (Ust'-Ishim), and modern humans (1000 Genomes). An average of 15 polymorphisms per individual were found in human populations (with a total of 262 polymorphisms). There were 94 polymorphisms identified across extinct Homo (an average of 13 per individual) with 41 previously observed in modern humans and 53 novel polymorphisms (32 in Denisova and 21 in Neandertal). Neither the frequency nor distribution of polymorphisms across gene regions exhibit significant differences within the genus Homo. Thus, humans are not unique with regards to the increased frequency of regulatory polymorphisms and the evolution of variation patterns across CCR5 gene appears to have originated within the genus. A broader evolutionary perspective on regulatory flexibility may be that it provided an advantage during the transition to confrontational foraging (and later hunting) that altered human-environment interaction as well as during migration to Eurasia and encounters with novel pathogens.}, }
@article {pmid30226838, year = {2018}, author = {Skov, L and Hui, R and Shchur, V and Hobolth, A and Scally, A and Schierup, MH and Durbin, R}, title = {Detecting archaic introgression using an unadmixed outgroup.}, journal = {PLoS genetics}, volume = {14}, number = {9}, pages = {e1007641}, doi = {10.1371/journal.pgen.1007641}, pmid = {30226838}, issn = {1553-7404}, abstract = {Human populations outside of Africa have experienced at least two bouts of introgression from archaic humans, from Neanderthals and Denisovans. In Papuans there is prior evidence of both these introgressions. Here we present a new approach to detect segments of individual genomes of archaic origin without using an archaic reference genome. The approach is based on a hidden Markov model that identifies genomic regions with a high density of single nucleotide variants (SNVs) not seen in unadmixed populations. We show using simulations that this provides a powerful approach to identifying segments of archaic introgression with a low rate of false detection, given data from a suitable outgroup population is available, without the archaic introgression but containing a majority of the variation that arose since initial separation from the archaic lineage. Furthermore our approach is able to infer admixture proportions and the times both of admixture and of initial divergence between the human and archaic populations. We apply the model to detect archaic introgression in 89 Papuans and show how the identified segments can be assigned to likely Neanderthal or Denisovan origin. We report more Denisovan admixture than previous studies and find a shift in size distribution of fragments of Neanderthal and Denisovan origin that is compatible with a difference in admixture time. Furthermore, we identify small amounts of Denisova ancestry in South East Asians and South Asians.}, }
@article {pmid30209350, year = {2018}, author = {Clyde, D}, title = {The girl with Neanderthal and Denisovan parents.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41576-018-0054-6}, pmid = {30209350}, issn = {1471-0064}, }
@article {pmid30185153, year = {2018}, author = {Dergunova, LV and Filippenkov, IB and Stavchansky, VV and Denisova, AE and Yuzhakov, VV and Mozerov, SA and Gubsky, LV and Limborska, SA}, title = {Genome-wide transcriptome analysis using RNA-Seq reveals a large number of differentially expressed genes in a transient MCAO rat model.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {655}, doi = {10.1186/s12864-018-5039-5}, pmid = {30185153}, issn = {1471-2164}, support = {16-14-00077//Russian Science Foundation/ ; }, abstract = {BACKGROUND: The transient middle cerebral artery occlusion (tMCAO) model is used for studying the molecular mechanisms of ischemic damage and neuroprotection. Numerous studies have demonstrated the role of individual genes and associated signaling pathways in the pathogenesis of ischemic stroke. Here, the tMCAO model was used to investigate the genome-wide response of the transcriptome of rat brain tissues to the damaging effect of ischemia and subsequent reperfusion.

RESULTS: Magnetic resonance imaging and histological examination showed that the model of focal ischemia based on endovascular occlusion of the right middle cerebral artery for 90 min using a monofilament, followed by restoration of the blood flow, led to reproducible localization of ischemic damage in the subcortical structures of the brain. High-throughput RNA sequencing (RNA-Seq) revealed the presence of differentially expressed genes (DEGs) in subcortical structures of rat brains resulting from hemisphere damage by ischemia after tMCAO, as well as in the corresponding parts of the brains of sham-operated animals. Real-time reverse transcription polymerase chain reaction expression analysis of 20 genes confirmed the RNA-Seq results. We identified 469 and 1939 genes that exhibited changes in expression of > 1.5-fold at 4.5 and 24 h after tMCAO, respectively. Interestingly, we found 2741 and 752 DEGs under ischemia-reperfusion and sham-operation conditions at 24 h vs. 4.5 h after tMCAO, respectively. The activation of a large number of genes involved in inflammatory, immune and stress responses, apoptosis, ribosome function, DNA replication and other processes was observed in ischemia-reperfusion conditions. Simultaneously, massive down-regulation of the mRNA levels of genes involved in the functioning of neurotransmitter systems was recorded. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that dozens of signaling pathways were associated with DEGs in ischemia-reperfusion conditions.

CONCLUSIONS: The data obtained revealed a global profile of gene expression in the rat brain sub-cortex under tMCAO conditions that can be used to identify potential therapeutic targets in the development of new strategies for the prevention and treatment of ischemic stroke.}, }
@article {pmid30149747, year = {2018}, author = {Alexeeva, E and Dvoryakovskaya, T and Denisova, R and Sleptsova, T and Isaeva, K and Chomahidze, A and Fetisova, A and Mamutova, A and Alshevskaya, A and Gladkikh, V and Moskalev, A}, title = {Comparative Analysis of the Etanercept Efficacy in Children with Juvenile Idiopathic Arthritis Under the Age of 4 Years and Children of Older Age Groups Using the Propensity Score Matching Method.}, journal = {Modern rheumatology}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/14397595.2018.1516329}, pmid = {30149747}, issn = {1439-7609}, abstract = {OBJECTIVE: The study aim was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the data with those for older age groups.

METHODS: Three groups comprising 34 patients each (the total number, 102 patients) were selected using the PSM method. The study group (patients under the age of 4 years; the Junior group (JNR)) were compared with patients of the older age groups adjusted for gender, JIA category, JIA severity, and either age at disease onset (the RAO group) or disease duration (the RDD group).

RESULTS: All three groups showed good response to ETA therapy. During the follow-up period, only 4 (3.9%) patients failed to reach ACR50. In the JNR group, 82.4% of patients achieved ACR90 within median time 3 months (IQR, 3 - 6 months), which was a better result compared to the other two groups: 61.8% (RAO group) and 58.8% (RDD group) of patients achieved ACR90 within 6 (IQR, 3 - 9) months (p = 0.028). Three (9%) patients in the JNR group and none of the RDD and RAO groups discontinued treatment because of clinical remission (p = 0.045).

CONCLUSION: An analysis of the ETA efficacy in different age groups comparable in terms of the diagnosis and disease severity demonstrated a higher efficacy of earlier ETA therapy in children of the same age at disease onset. In children at the early stage of arthritis (≤ 2.5 years long), ETA was more efficient in those with an earlier disease onset.}, }
@article {pmid30135579, year = {2018}, author = {Slon, V and Mafessoni, F and Vernot, B and de Filippo, C and Grote, S and Viola, B and Hajdinjak, M and Peyrégne, S and Nagel, S and Brown, S and Douka, K and Higham, T and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Kelso, J and Meyer, M and Prüfer, K and Pääbo, S}, title = {The genome of the offspring of a Neanderthal mother and a Denisovan father.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41586-018-0455-x}, pmid = {30135579}, issn = {1476-4687}, abstract = {Neanderthals and Denisovans are extinct groups of hominins that separated from each other more than 390,000 years ago1,2. Here we present the genome of 'Denisova 11', a bone fragment from Denisova Cave (Russia)3 and show that it comes from an individual who had a Neanderthal mother and a Denisovan father. The father, whose genome bears traces of Neanderthal ancestry, came from a population related to a later Denisovan found in the cave4-6. The mother came from a population more closely related to Neanderthals who lived later in Europe2,7 than to an earlier Neanderthal found in Denisova Cave8, suggesting that migrations of Neanderthals between eastern and western Eurasia occurred sometime after 120,000 years ago. The finding of a first-generation Neanderthal-Denisovan offspring among the small number of archaic specimens sequenced to date suggests that mixing between Late Pleistocene hominin groups was common when they met.}, }
@article {pmid30135540, year = {2018}, author = {Warren, M}, title = {Mum's a Neanderthal, Dad's a Denisovan: First discovery of an ancient-human hybrid.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {417-418}, doi = {10.1038/d41586-018-06004-0}, pmid = {30135540}, issn = {1476-4687}, }
@article {pmid30121933, year = {2018}, author = {Zotova, TY and Blagonravov, ML and Lapaev, NN and Denisova, AP}, title = {Hemodynamic Allostasis of Pregnant Women against the Background of Preeclampsia.}, journal = {Bulletin of experimental biology and medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10517-018-4189-4}, pmid = {30121933}, issn = {1573-8221}, abstract = {We analyzed diurnal hemodynamic parameters (HR, systolic BP, and diastolic BP) recorded from two groups of edematous and preeclamptic pregnant women. The unidirectional character of changes in the control over the functional state of cardiovascular system was revealed except for the indices, which mark a pathological process: elevated diurnal BP in preeclampsia and diminished percentage of oscillation power in edematous patients. Uniformity of the regulatory changes in patients with and without arterial hypertension can be viewed as manifestation of allostasis developed by the cardiovascular system during pregnancy. In preeclampsia, the greater allostatic load was reflected by the changes in diurnal, daytime, and nighttime BP and in the circadian index calculated for HR, systolic BP, and diastolic BP. In edematous patients, elevation of allostatic load was indicated by the percentage of ultradian rhythms.}, }
@article {pmid30076299, year = {2018}, author = {Helsen, CW and Hammill, JA and Lau, VWC and Mwawasi, KA and Afsahi, A and Bezverbnaya, K and Newhook, L and Hayes, DL and Aarts, C and Bojovic, B and Denisova, GF and Kwiecien, JM and Brain, I and Derocher, H and Milne, K and Nelson, BH and Bramson, JL}, title = {The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {3049}, doi = {10.1038/s41467-018-05395-y}, pmid = {30076299}, issn = {2041-1723}, abstract = {Engineering T cells with chimeric antigen receptors (CARs) is an effective method for directing T cells to attack tumors, but may cause adverse side effects such as the potentially lethal cytokine release syndrome. Here the authors show that the T cell antigen coupler (TAC), a chimeric receptor that co-opts the endogenous TCR, induces more efficient anti-tumor responses and reduced toxicity when compared with past-generation CARs. TAC-engineered T cells induce robust and antigen-specific cytokine production and cytotoxicity in vitro, and strong anti-tumor activity in a variety of xenograft models including solid and liquid tumors. In a solid tumor model, TAC-T cells outperform CD28-based CAR-T cells with increased anti-tumor efficacy, reduced toxicity, and faster tumor infiltration. Intratumoral TAC-T cells are enriched for Ki-67+ CD8+ T cells, demonstrating local expansion. These results indicate that TAC-T cells may have a superior therapeutic index relative to CAR-T cells.}, }
@article {pmid30064273, year = {2018}, author = {Morgunov, LY and Denisova, IA and Rozhkova, TI and Stakhovskaya, LV and Skvortsova, VI}, title = {Hypogonadism and its treatment following ischaemic stroke in men with type 2 diabetes mellitus.}, journal = {The aging male : the official journal of the International Society for the Study of the Aging Male}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/13685538.2018.1487932}, pmid = {30064273}, issn = {1473-0790}, abstract = {Premature mortality in Russia is a major socio-economic problem, especially from acute cerebrovascular diseases which constitute 21.4% of the total mortality and is a considerable contributor to chronic disability. Risk of vascular catastrophe is higher in males than females, thought, in part, due to anti-atherosclerotic effects of oestrogens in females whilst an associated age-related deficiency of testosterone is observed in men. Clinical symptoms such as high blood pressure, changes in lipid profile, insulin resistance, obesity, and blood coagulation factors often accompany declining testosterone in males and reduced total testosterone is considered a cardiovascular risk factor. In the present study, the prevalence of hypogonadism in men who had suffered ischaemic stroke was evaluated along with the efficacy of testosterone undecanoate injections (TU) in patients with testosterone deficiency and type-2 diabetes (T2DM) in the acute phase of hemispheric ischaemic stroke. Hypogonadism was present in 66.3% of patients with ischaemic stroke, 50% with T2DM, and 26.3% without T2DM, respectively. TU treatment, at both the 2 and 5-year observation points, demonstrated significant improvements in biochemical, physical, and mental parameters. This supports that testosterone deficiency is a contributing factor in ischaemic events and that long-term testosterone therapy could play an important role in patient recovery.}, }
@article {pmid30022013, year = {2018}, author = {Dolgova, O and Lao, O}, title = {Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes.}, journal = {Genes}, volume = {9}, number = {7}, pages = {}, doi = {10.3390/genes9070358}, pmid = {30022013}, issn = {2073-4425}, abstract = {The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered. It is currently known that AMH interbred with archaic hominins once they left the African continent. Current non-African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.}, }
@article {pmid30010009, year = {2018}, author = {Denisova, K}, title = {Neurobiology, not artifacts: Challenges and guidelines for imaging the high risk infant.}, journal = {NeuroImage}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroimage.2018.07.023}, pmid = {30010009}, issn = {1095-9572}, abstract = {The search for the brain-basis of atypical development in human infants is challenging because the process of imaging and the generation of the MR signal itself relies on assumptions that reflect biophysical properties of the brain tissue. These assumptions are not inviolate, have been questioned by recent empirical evidence from high risk infant-sibling studies, and to date remain largely under-examined at the between-group level. In particular, I consider recent work showing that infants at High vs. Low familial risk (HR vs. LR, respectively) for developing Autism Spectrum Disorders (ASD) have atypical patterns of head movements during an MR scan that are functionally important-they are linked to future learning trajectories in toddlerhood. Addressing head movement issues in neuroimaging analyses in infant research as well as understanding the causes of these movements from a developmental perspective requires acknowledging the complexity of this endeavor. For example, head movement signatures in infants can interact with experimental task conditions (such as listening to language compared to sleeping), autism risk, and age. How can new knowledge about newborns' individual, subject-specific behavioral differences which may impact MR signal acquisition and statistical inference ignite critical thinking for the field of infant brain imaging across the spectrum of typical and atypical development? Early behavioral differences between HR and LR infant cohorts that are often examples of "artifactual" confounds in MR work provide insight into nascent neurobiological differences, including biophysical tissue properties and hemodynamic response variability, in these and related populations at risk for atypical development. Are these neurobiological drivers of atypical development? This work identifies important knowledge gaps and suggests guidelines at the leading edge of baby imaging science to transform our understanding of atypical brain development in humans. The precise study of the neurobiological underpinnings of atypical development in humans calls for approaches including quantitative MRI (qMRI) pulse sequences, multi-modal imaging (including DTI, MRS, as well as MEG), and infant-specific HRF shapes when modeling BOLD signal.}, }
@article {pmid30004998, year = {2018}, author = {Raevis, JJ and Denisova, K and Mechel, E and Shrier, EM}, title = {MOSAICISM AS A PROPOSED MECHANISM FOR ASYMMETRIC RETINAL TESSELLATIONS.}, journal = {Retinal cases & brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000000770}, pmid = {30004998}, issn = {1937-1578}, abstract = {BACKGROUND/PURPOSE: Report a case of markedly asymmetric retinal tessellations and propose mosaicism as a mechanism.

METHODS AND RESULTS: A 59-year-old pseudophakic woman presented with uncorrected 20/20 vision and was found to have markedly different retinal tessellation appearances in both eyes. The axial lengths were 25.66 mm and 25.88 mm in the right and left eyes, respectively, and no significant asymmetrical choroidal thinning was seen on optical coherence tomography or optical coherence tomography angiography. Fluorescein angiogram showed significant hyperfluorescence, representing the underlying choroid, which correlated with the tessellation patterns in the left eye. She had no other ocular or systemic findings such as stripes or whorled skin.

CONCLUSION: This is the first reported case of markedly asymmetric retinal tessellation patterns that are not due to asymmetric axial myopia or choroidal thinning. We propose that mosaicism is a possible mechanism causing this finding.}, }
@article {pmid29995885, year = {2018}, author = {Zhao, G and Walsh, K and Long, J and Gui, W and Denisova, K}, title = {Reduced structural complexity of the right cerebellar cortex in male children with autism spectrum disorder.}, journal = {PloS one}, volume = {13}, number = {7}, pages = {e0196964}, doi = {10.1371/journal.pone.0196964}, pmid = {29995885}, issn = {1932-6203}, abstract = {The cerebellum contains 80% of all neurons in the human brain and contributes prominently to implicit learning and predictive processing across motor, sensory, and cognitive domains. As morphological features of the cerebellum in atypically developing individuals remain unexplored in-vivo, this is the first study to use high-resolution 3D fractal analysis to estimate fractal dimension (FD), a measure of structural complexity of an object, of the left and right cerebellar cortex (automatically segmented from Magnetic Resonance Images using FreeSurfer), in male children with Autism Spectrum Disorders (ASD) (N = 20; mean age: 8.8 years old, range: 7.13-10.27) and sex, age, verbal-IQ, and cerebellar volume-matched typically developing (TD) boys (N = 18; mean age: 8.9 years old, range: 6.47-10.52). We focus on an age range within the 'middle and late childhood' period of brain development, between 6 and 12 years. A Mann-Whitney U test revealed a significant reduction in the FD of the right cerebellar cortex in ASD relative to TD boys (P = 0.0063, Bonferroni-corrected), indicating flatter and less regular surface protrusions in ASD relative to TD males. Consistent with the prediction that the cerebellum participates in implicit learning, those ASD boys with a higher (vs. lower) PIQ>VIQ difference showed higher, more normative complexity values, closer to TD children, providing new insight on our understanding of the neurological basis of differences in verbal and performance cognitive abilities that often characterize individuals with ASD.}, }
@article {pmid29948329, year = {2018}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Litvinov, A and Rogalla, U and Skonieczna, K and Grzybowski, T and Pentelényi, K and Guba, Z and Zeke, T and Molnár, MJ}, title = {Whole mitochondrial genome diversity in two Hungarian populations.}, journal = {Molecular genetics and genomics : MGG}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00438-018-1458-x}, pmid = {29948329}, issn = {1617-4623}, support = {16-34-00014//Russian Foundation for Basic Research/ ; ICRG-117//the Wenner-Gren Foundation/ ; }, abstract = {Complete mitochondrial genomics is an effective tool for studying the demographic history of human populations, but there is still a deficit of mitogenomic data in European populations. In this paper, we present results of study of variability of 80 complete mitochondrial genomes in two Hungarian populations from eastern part of Hungary (Szeged and Debrecen areas). The genetic diversity of Hungarian mitogenomes is remarkably high, reaching 99.9% in a combined sample. According to the analysis of molecular variance (AMOVA), European populations showed a low, but statistically significant level of between-population differentiation (Fst = 0.61%, p = 0), and two Hungarian populations demonstrate lack of between-population differences. Phylogeographic analysis allowed us to identify 71 different mtDNA sub-clades in Hungarians, sixteen of which are novel. Analysis of ancestry-informative mtDNA sub-clades revealed a complex genetic structure associated with the genetic impact of populations from different parts of Eurasia, though the contribution from European populations is the most pronounced. At least 8% of ancestry-informative haplotypes found in Hungarians demonstrate similarity with East and West Slavic populations (sub-clades H1c23a, H2a1c1, J2b1a6, T2b25a1, U4a2e, K1c1j, and I1a1c), while the influence of Siberian populations is not so noticeable (sub-clades A12a, C4a1a, and probably U4b1a4).}, }
@article {pmid29927400, year = {2018}, author = {Rzaev, DA and Denisova, NP and Moisak, GI and Rogov, DY and Kulikova, EV}, title = {[Experience of the use of gasserian ganglion balloon compression in patients with trigeminal neuralgia associated with multiple sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {118}, number = {5}, pages = {30-35}, doi = {10.17116/jnevro20181185130}, pmid = {29927400}, issn = {1997-7298}, abstract = {AIM: To evaluate the efficacy of gasserian ganglion balloon compression in patients with trigeminal neuralgia associated with multiple sclerosis (MS).

MATERIAL AND METHODS: Eight patients (3 men, 5 women), aged from 46 to 66 years (mean age 55 years), with trigeminal neuralgia associated with MS underwent surgery. An average duration of the pain syndrome was 8,4 years. Six patients had previous surgeries due to facial pain. Percutaneous balloon compression of gasserian ganglion was performed to all patients. Follow up period was from 2 to 24 months.

RESULTS: Six patients (75%) reported 100% of pain relief right after the surgery, 2 patients (25%) reported a significant decrease of pain (2-3 points on VAS). Pain recurrence occurred in 3 patients: in 4 months, in 12 months and in 6 months. All of them were operated repeatedly. After the surgery, hypoesthesia on the side of surgery was observed in all patients with a trend towards regression. There was no keratopathy or any complications.

CONCLUSION: Percutaneous balloon compression of gasserian ganglion is an effective and minimally invasive method which can be performed repeatedly in patients with trigeminal neuralgia associated with MS.}, }
@article {pmid29914355, year = {2018}, author = {Cserhati, MF and Mooter, ME and Peterson, L and Wicks, B and Xiao, P and Pauley, M and Guda, C}, title = {Motifome comparison between modern human, Neanderthal and Denisovan.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {472}, doi = {10.1186/s12864-018-4710-1}, pmid = {29914355}, issn = {1471-2164}, support = {P20 GM103427/GM/NIGMS NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; 2P20GM103427//Nebraska INBRE/ ; 5P30CA036727//CCSG award/ ; }, abstract = {BACKGROUND: The availability of the genomes of two archaic humans, Neanderthal and Denisovan, and that of modern humans provides researchers an opportunity to investigate genetic differences between these three subspecies on a genome-wide scale. Here we describe an algorithm that predicts statistically significant motifs based on the difference between a given motif's actual and expected distributions. The algorithm was previously applied to plants but was modified for this work.

RESULTS: The result of applying the algorithm to the human, Neanderthal, and Denisovan genomes is a catalog of potential regulatory motifs in these three human subspecies. We examined the distributions of these motifs in genetic elements including human retroviruses, human accelerated regions, and human accelerated conserved noncoding sequences regions. Differences in these distributions could be the origin of differences in phenotype between the three subspecies. Twenty significant motifs common to all three genomes were found; thirty-three were found in endogenous retroviruses in Neanderthal and Denisovan. Ten of these motifs mapped to the 22 bp core of MiR-1304. The core of this genetic element regulates the ENAM and AMTN genes, which take part in odontogenesis and whose 3' UTRs contained significant motifs. The introns of 20 genes were found to contain a large number of significant motifs, which were also overrepresented in 49 human accelerated regions. These genes include NAV2, SorCS2, TRAPPC9, GRID1, PRDM16, CAMTA1, and ASIC which are all involved in neuroregulation. Further analysis of these genes using the GO database indicates that many are associated with neurodevelopment. Also, varying numbers of significant motifs were found to occur in regions of the Neanderthal and Denisovan genomes that are missing from the human genome, suggesting further functional differences between modern and archaic humans.

CONCLUSION: Although Neanderthal and Denisovan are now extinct, detailed examination of elements from their genomes can shed light on possible phenotypic and cognitive differences between these two archaic human subspecies and modern humans. Genetic similarities and differences between these three subspecies and other fossil hominids would also be of interest.}, }
@article {pmid29747567, year = {2018}, author = {Banerjee, N and Polushina, T and Bettella, F and Giddaluru, S and Steen, VM and Andreassen, OA and Le Hellard, S}, title = {Recently evolved human-specific methylated regions are enriched in schizophrenia signals.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {63}, doi = {10.1186/s12862-018-1177-2}, pmid = {29747567}, issn = {1471-2148}, support = {#2 T23273//Norges Forskningsråd/ ; SKGJ-MED-008//KG Jebsen Foundation/ ; }, abstract = {BACKGROUND: One explanation for the persistence of schizophrenia despite the reduced fertility of patients is that it is a by-product of recent human evolution. This hypothesis is supported by evidence suggesting that recently-evolved genomic regions in humans are involved in the genetic risk for schizophrenia. Using summary statistics from genome-wide association studies (GWAS) of schizophrenia and 11 other phenotypes, we tested for enrichment of association with GWAS traits in regions that have undergone methylation changes in the human lineage compared to Neanderthals and Denisovans, i.e. human-specific differentially methylated regions (DMRs). We used analytical tools that evaluate polygenic enrichment of a subset of genomic variants against all variants.

RESULTS: Schizophrenia was the only trait in which DMR SNPs showed clear enrichment of association that passed the genome-wide significance threshold. The enrichment was not observed for Neanderthal or Denisovan DMRs. The enrichment seen in human DMRs is comparable to that for genomic regions tagged by Neanderthal Selective Sweep markers, and stronger than that for Human Accelerated Regions. The enrichment survives multiple testing performed through permutation (n = 10,000) and bootstrapping (n = 5000) in INRICH (p < 0.01). Some enrichment of association with height was observed at the gene level.

CONCLUSIONS: Regions where DNA methylation modifications have changed during recent human evolution show enrichment of association with schizophrenia and possibly with height. Our study further supports the hypothesis that genetic variants conferring risk of schizophrenia co-occur in genomic regions that have changed as the human species evolved. Since methylation is an epigenetic mark, potentially mediated by environmental changes, our results also suggest that interaction with the environment might have contributed to that association.}, }
@article {pmid29739306, year = {2018}, author = {Akkuratov, EE and Gelfand, MS and Khrameeva, EE}, title = {Neanderthal and Denisovan ancestry in Papuans: A functional study.}, journal = {Journal of bioinformatics and computational biology}, volume = {16}, number = {2}, pages = {1840011}, doi = {10.1142/S0219720018400115}, pmid = {29739306}, issn = {1757-6334}, abstract = {Sequencing of complete nuclear genomes of Neanderthal and Denisovan stimulated studies about their relationship with modern humans demonstrating, in particular, that DNA alleles from both Neanderthal and Denisovan genomes are present in genomes of modern humans. The Papuan genome is a unique object because it contains both Neanderthal and Denisovan alleles. Here, we have shown that the Papuan genomes contain different gene functional groups inherited from each of the ancient people. The Papuan genomes demonstrate a relative prevalence of Neanderthal alleles in genes responsible for the regulation of transcription and neurogenesis. The enrichment of specific functional groups with Denisovan alleles is less pronounced; these groups are responsible for bone and tissue remodeling. This analysis shows that introgression of alleles from Neanderthals and Denisovans to Papuans occurred independently and retention of these alleles may carry specific adaptive advantages.}, }
@article {pmid29688213, year = {2018}, author = {Shkliaev, AE and Denisova, NI and Kulikov, IV}, title = {[Splenic artery aneurysm masked by postcholecystectomy syndrome].}, journal = {Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery}, volume = {24}, number = {1}, pages = {175-178}, pmid = {29688213}, issn = {1027-6661}, mesh = {*Aneurysm/diagnosis/physiopathology/surgery ; Angiography/methods ; Blood Vessel Prosthesis Implantation/*methods ; Diagnosis, Differential ; Endovascular Procedures/*methods ; Female ; Humans ; Middle Aged ; Postcholecystectomy Syndrome/*diagnosis ; *Splenic Artery/diagnostic imaging/pathology ; Tomography, Spiral Computed/methods ; Treatment Outcome ; }, abstract = {Visceral artery aneurysms appear to belong to uncommon and potentially lethal vascular diseases. They are usually revealed accidentally during an ultrasonographic examination, magnetic resonance imaging, or computed tomography. Described in the article is a clinical case report concerning a sacciform aneurysm of the splenic artery, detected in a 53-year-old woman presenting with postcholecystectomy syndrome and followed up for abdominalgia by therapeutists and gastroenterologists. Timely performed radiodiagnosis (including multispiral computed tomography and angiography of the abdominal vessels) made it possible not only to detect the aneurysm, having thus verified the volumetric formation previously found on ultrasonographic examination, but to take adequate measures aimed at preventing rupture of the aneurysm and consisting in endovascular occlusion of the aneurysmatic cavity with metal spirals. Lack of complete clarity in the understanding of the mechanisms of the origin of and no distinctly defined therapeutic-and-diagnostic algorithm for visceral artery aneurysms dictate the necessity to continue collecting and generalizing clinical case reports regarding this rarely encountered vascular pathology.}, }
@article {pmid29667630, year = {2018}, author = {Bogomolov, DV and Fetisov, VA and Denisova, OP and Zbrueva, YV and Semenov, GG}, title = {[The principal and auxiliary immunohistochemical markers of intravital mechanical strangulation asphyxia].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {61}, number = {2}, pages = {11-13}, doi = {10.17116/sudmed201861211-13}, pmid = {29667630}, issn = {0039-4521}, abstract = {The objective of the present study was the evaluation of the auxiliary methods for the diagnostics of the intravital formation of the constriction marks; the secondary objective was to determine the pace at which the death and asphyxia occur.

MATERIAL AND METHODS: The materials on which the study was based included 17 cases of mechanical strangulation asphyxia involving 13 men and 4 women at the age from 8 to 28 years. All cases of hanging were associated with different blood alcohol levels. Their characteristic feature was the formation of the obliquely ascending constriction marks. The group of comparison was comprised of three cases of death by drowning and one case of manual strangulation. The control group consisted of 10 patients who died from the acute form of coronary heart disease and 5 cases of death from traumatic shock. All the corpses were examined with the use of the traditional methods within the first 24 hours after death. The special laboratory studies were performed by means of the standard histological and immunohistochemical methods with the use of the polyclonal antibodies against total cytokeratin, fibrinogen, immunoglobulin-lambda, fibronectin, and CD-117 antigen. The histological preparations were stained by the method of Spielmeyer and with toluidine blue.

RESULTS: The results of the study give evidence of the possibility of diagnostics of mechanical strangulation asphyxia making use of the reaction with anti-fibrinogen antibodies in the stromal tissue of the constriction mark even in the absence of other intravital signs of death. Such diagnostics is also possible with the use of the CD-117 antigen in the pulmonary tissue. The expression of this antigen is characteristic of the cases of alveolar hypoxia. The possibility of application of other markers for the differential diagnostics of mechanical strangulation asphyxia from other causes of death is discussed.}, }
@article {pmid29659494, year = {2018}, author = {Khabarova, EA and Denisova, NP and Dmitriev, AB and Slavin, KV and Verhagen Metman, L}, title = {Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson Disease with Prior Pallidotomy or Thalamotomy.}, journal = {Brain sciences}, volume = {8}, number = {4}, pages = {}, doi = {10.3390/brainsci8040066}, pmid = {29659494}, issn = {2076-3425}, abstract = {Objective. To evaluate the efficacy of deep brain stimulation of the subthalamic nucleus (STN DBS) in patients with Parkinson disease (PD) who previously underwent lesioning of the basal ganglia. Material and methods. The study included 22 patients who underwent STN DBS. Eleven patients had undergone prior unilateral pallidotomy (n = 6) or VL/VIM thalamotomy (n = 5) while the other 11 patients had not. The primary outcome was the change from baseline in the motor subscore of the Unified Parkinson Disease Rating Scale (UPDRS-III) 12 months after STN DBS. Secondary outcomes included change in motor response complications (UPDRS-IV) and change in levodopa equivalent daily dose (LEDD). Results. In the group with prior lesioning UPDRS-III improved by 45%, from 51.5 &plusmn; 9.0% (range, 35&ndash;65) to 26.5 &plusmn; 8.4 (range, 21&ndash;50) (p < 0.01) and UPDRS-IV by 75%, from 8.0 &plusmn; 2.01 (range, 5&ndash;11) to 2.1 &plusmn; 0.74 (range, 1&ndash;3) (p < 0.01). In the group without prior lesioning UPDRS-III improved by 61%, from 74.2% &plusmn; 7.32 (range, 63&ndash;82) to 29.3 &plusmn; 5.99 (range, 20&ndash;42) (p < 0.01) and UPDRS-IV by 77%, from 9.1 &plusmn; 2.46 (range, 5&ndash;12) to 2.0 &plusmn; 1.1 (range, 1&ndash;4) (p < 0.01). Comparing the two groups (with and without lesioning) no significant differences were found either in UPDRS-III (p > 0.05) or UPDRS-IV scores (p > 0.05) at 12 months post-DBS. The LEDD was reduced by 51.4%, from 1008.2 &plusmn; 346.4 to 490.0 &plusmn; 194.3 in those with prior surgery (p < 0.01) and by 55.0%, from 963.4 &plusmn; 96.2 to 433.3 &plusmn; 160.2 in those without (p < 0.01).UPDRS-III improved by 51.8%, from 53.7 &plusmn; 4.6 (range, 50&ndash;62) to 25.0 &plusmn; 3.8 (range, 21&ndash;31) in those with prior pallidotomy (p < 0.01), and by 37.5%, from 48.8 &plusmn; 12.6 (range, 35&ndash;65) to 29.8 &plusmn; 13.6 (range, 22&ndash;50) in those with prior thalamotomy (p < 0.01). This numerical difference in improvement was not statistically significant (p > 0.05). Conclusion. Our comparative study indicates that bilateral STN DBS is effective and can be used in patients with Parkinson disease with prior unilateral stereotactic destructive operations on subcortical structures. The results in our patient cohort are generally consistent with previously published reports of smaller series from multiple centers worldwide.}, }
@article {pmid29658973, year = {2018}, author = {Viscardi, LH and Paixão-Côrtes, VR and Comas, D and Salzano, FM and Rovaris, D and Bau, CD and Amorim, CEG and Bortolini, MC}, title = {Searching for ancient balanced polymorphisms shared between Neanderthals and Modern Humans.}, journal = {Genetics and molecular biology}, volume = {41}, number = {1}, pages = {67-81}, doi = {10.1590/1678-4685-GMB-2017-0308}, pmid = {29658973}, issn = {1415-4757}, abstract = {Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of trans-SNP in two gene sets: one associated with the immune system (IMMS) and another one with behavioral system (BEHS). We identified a significant excess of trans-SNPs in IMMS (N=547), of which six of these located within genes previously associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but five genes in this system harbor potential signals for balancing selection and are associated with psychiatric or neurodevelopmental disorders. Our approach evidenced recent Homo trans-SNPs that have been previously implicated in psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire common to the immune and behavioral systems could have been maintained by balancing selection starting before the split between archaic and modern humans.}, }
@article {pmid29608725, year = {2018}, author = {Zehra, R and Abbasi, AA}, title = {Homo sapiens-Specific Binding Site Variants within Brain Exclusive Enhancers Are Subject to Accelerated Divergence across Human Population.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {956-966}, doi = {10.1093/gbe/evy052}, pmid = {29608725}, issn = {1759-6653}, abstract = {Empirical assessments of human accelerated noncoding DNA frgaments have delineated presence of many cis-regulatory elements. Enhancers make up an important category of such accelerated cis-regulatory elements that efficiently control the spatiotemporal expression of many developmental genes. Establishing plausible reasons for accelerated enhancer sequence divergence in Homo sapiens has been termed significant in various previously published studies. This acceleration by including closely related primates and archaic human data has the potential to open up evolutionary avenues for deducing present-day brain structure. This study relied on empirically confirmed brain exclusive enhancers to avoid any misjudgments about their regulatory status and categorized among them a subset of enhancers with an exceptionally accelerated rate of lineage specific divergence in humans. In this assorted set, 13 distinct transcription factor binding sites were located that possessed unique existence in humans. Three of 13 such sites belonging to transcription factors SOX2, RUNX1/3, and FOS/JUND possessed single nucleotide variants that made them unique to H. sapiens upon comparisons with Neandertal and Denisovan orthologous sequences. These variants modifying the binding sites in modern human lineage were further substantiated as single nucleotide polymorphisms via exploiting 1000 Genomes Project Phase3 data. Long range haplotype based tests laid out evidence of positive selection to be governing in African population on two of the modern human motif modifying alleles with strongest results for SOX2 binding site. In sum, our study acknowledges acceleration in noncoding regulatory landscape of the genome and highlights functional parts within it to have undergone accelerated divergence in present-day human population.}, }
@article {pmid29570998, year = {2018}, author = {Vernot, B and Pääbo, S}, title = {The Predecessors Within . . .}, journal = {Cell}, volume = {173}, number = {1}, pages = {6-7}, doi = {10.1016/j.cell.2018.03.023}, pmid = {29570998}, issn = {1097-4172}, abstract = {By examining the genomes of present-day people from Asia, researchers show that modern humans met and interbred with Denisovans, distant relatives to Neanderthals, on at least two occasions. As a result, people today carry DNA from two different Denisovan populations.}, }
@article {pmid29551270, year = {2018}, author = {Browning, SR and Browning, BL and Zhou, Y and Tucci, S and Akey, JM}, title = {Analysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture.}, journal = {Cell}, volume = {173}, number = {1}, pages = {53-61.e9}, doi = {10.1016/j.cell.2018.02.031}, pmid = {29551270}, issn = {1097-4172}, support = {R01 GM110068/GM/NIGMS NIH HHS/United States ; }, abstract = {Anatomically modern humans interbred with Neanderthals and with a related archaic population known as Denisovans. Genomes of several Neanderthals and one Denisovan have been sequenced, and these reference genomes have been used to detect introgressed genetic material in present-day human genomes. Segments of introgression also can be detected without use of reference genomes, and doing so can be advantageous for finding introgressed segments that are less closely related to the sequenced archaic genomes. We apply a new reference-free method for detecting archaic introgression to 5,639 whole-genome sequences from Eurasia and Oceania. We find Denisovan ancestry in populations from East and South Asia and Papuans. Denisovan ancestry comprises two components with differing similarity to the sequenced Altai Denisovan individual. This indicates that at least two distinct instances of Denisovan admixture into modern humans occurred, involving Denisovan populations that had different levels of relatedness to the sequenced Altai Denisovan. VIDEO ABSTRACT.}, }
@article {pmid29477182, year = {2018}, author = {Warren, KA and Ritzman, TB and Humphreys, RA and Percival, CJ and Hallgrímsson, B and Ackermann, RR}, title = {Craniomandibular form and body size variation of first generation mouse hybrids: A model for hominin hybridization.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {57-74}, doi = {10.1016/j.jhevol.2017.12.002}, pmid = {29477182}, issn = {1095-8606}, abstract = {Hybridization occurs in a number of mammalian lineages, including among primate taxa. Analyses of ancient genomes have shown that hybridization between our lineage and other archaic hominins in Eurasia occurred numerous times in the past. However, we still have limited empirical data on what a hybrid skeleton looks like, or how to spot patterns of hybridization among fossils for which there are no genetic data. Here we use experimental mouse models to supplement previous studies of primates. We characterize size and shape variation in the cranium and mandible of three wild-derived inbred mouse strains and their first generation (F1) hybrids. The three parent taxa in our analysis represent lineages that diverged over approximately the same period as the human/Neanderthal/Denisovan lineages and their hybrids are variably successful in the wild. Comparisons of body size, as quantified by long bone measurements, are also presented to determine whether the identified phenotypic effects of hybridization are localized to the cranium or represent overall body size changes. The results indicate that hybrid cranial and mandibular sizes, as well as limb length, exceed that of the parent taxa in all cases. All three F1 hybrid crosses display similar patterns of size and form variation. These results are generally consistent with earlier studies on primates and other mammals, suggesting that the effects of hybridization may be similar across very different scenarios of hybridization, including different levels of hybrid fitness. This paper serves to supplement previous studies aimed at identifying F1 hybrids in the fossil record and to introduce further research that will explore hybrid morphologies using mice as a proxy for better understanding hybridization in the hominin fossil record.}, }
@article {pmid29445326, year = {2018}, author = {Leacock, S and Syed, P and James, VM and Bode, A and Kawakami, K and Keramidas, A and Suster, M and Lynch, JW and Harvey, RJ}, title = {Structure/Function Studies of the α4 Subunit Reveal Evolutionary Loss of a GlyR Subtype Involved in Startle and Escape Responses.}, journal = {Frontiers in molecular neuroscience}, volume = {11}, number = {}, pages = {23}, doi = {10.3389/fnmol.2018.00023}, pmid = {29445326}, issn = {1662-5099}, support = {MR/J004049/1//Medical Research Council/United Kingdom ; }, abstract = {Inhibitory glycine receptors (GlyRs) are pentameric ligand-gated anion channels with major roles in startle disease/hyperekplexia (GlyR α1), cortical neuronal migration/autism spectrum disorder (GlyR α2), and inflammatory pain sensitization/rhythmic breathing (GlyR α3). However, the role of the GlyR α4 subunit has remained enigmatic, because the corresponding human gene (GLRA4) is thought to be a pseudogene due to an in-frame stop codon at position 390 within the fourth membrane-spanning domain (M4). Despite this, a recent genetic study has implicated GLRA4 in intellectual disability, behavioral problems and craniofacial anomalies. Analyzing data from sequenced genomes, we found that GlyR α4 subunit genes are predicted to be intact and functional in the majority of vertebrate species-with the exception of humans. Cloning of human GlyR α4 cDNAs excluded alternative splicing and RNA editing as mechanisms for restoring a full-length GlyR α4 subunit. Moreover, artificial restoration of the missing conserved arginine (R390) in the human cDNA was not sufficient to restore GlyR α4 function. Further bioinformatic and mutagenesis analysis revealed an additional damaging substitution at K59 that ablates human GlyR α4 function, which is not present in other vertebrate GlyR α4 sequences. The substitutions K59 and X390 were also present in the genome of an ancient Denisovan individual, indicating that GLRA4 has been a pseudogene for at least 30,000-50,000 years. In artificial synapses, we found that both mouse and gorilla α4β GlyRs mediate synaptic currents with unusually slow decay kinetics. Lastly, to gain insights into the biological role of GlyR α4 function, we studied the duplicated genes glra4a and glra4b in zebrafish. While glra4b expression is restricted to the retina, using a novel tol2-GAL4FF gene trap line (SAIGFF16B), we found that the zebrafish GlyR α4a subunit gene (glra4a) is strongly expressed in spinal cord and hindbrain commissural neurones. Using gene knockdown and a dominant-negative GlyR α4aR278Q mutant, we found that GlyR α4a contributes to touch-evoked escape behaviors in zebrafish. Thus, although GlyR α4 is unlikely to be involved in human startle responses or disease states, this subtype may contribute to escape behaviors in other organisms.}, }
@article {pmid29428968, year = {2018}, author = {Jiang, L and Peng, J and Huang, M and Liu, J and Wang, L and Ma, Q and Zhao, H and Yang, X and Ji, A and Li, C}, title = {Differentiation analysis for estimating individual ancestry from the Tibetan Plateau by an archaic altitude adaptation EPAS1 haplotype among East Asian populations.}, journal = {International journal of legal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00414-018-1789-5}, pmid = {29428968}, issn = {1437-1596}, support = {2017YFC0803501//National Key Research and Development Program of China/ ; 2016JB039//basic research project/ ; 2017JB027//basic research project/ ; }, abstract = {Tibetans have adapted to the extreme environment of high altitude for hundreds of generations. A highly differentiated 5-SNP (Single Nucleotide Polymorphism) haplotype motif (AGGAA) on a hypoxic pathway gene, EPAS1, is observed in Tibetans and lowlanders. To evaluate the potential usage of the 5-SNP haplotype in ancestry inference for Tibetan or Tibetan-related populations, we analyzed this haplotype in 1053 individuals of 12 Chinese populations residing on the Tibetan Plateau, peripheral regions of Tibet, and plain regions. These data were integrated with the genotypes from the 1000 Genome populations and populations in a previously reported paper for population structure analyses. We found that populations representing highland and lowland groups have different dominant ancestry components. The core Denisovan haplotype (AGGAA) was observed at a frequency of 72.32% in the Tibetan Plateau, with a frequency range from 9.48 to 21.05% in the peripheral regions and < 2.5% in the plains area. From the individual perspective, 87.57% of the individuals from the Tibetan Plateau carried the archaic haplotype, while < 5% of the Chinese Han people carried the haplotype. Our findings indicate that the 5-SNP haplotype has a special distribution pattern in populations of Tibet and peripheral regions and could be integrated into AISNP (Ancestry Informative Single Nucleotide Polymorphism) panels to enhance ancestry resolution.}, }
@article {pmid29422656, year = {2018}, author = {Rodríguez-Paredes, M and Bormann, F and Raddatz, G and Gutekunst, J and Lucena-Porcel, C and Köhler, F and Wurzer, E and Schmidt, K and Gallinat, S and Wenck, H and Röwert-Huber, J and Denisova, E and Feuerbach, L and Park, J and Brors, B and Herpel, E and Nindl, I and Hofmann, TG and Winnefeld, M and Lyko, F}, title = {Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {577}, doi = {10.1038/s41467-018-03025-1}, pmid = {29422656}, issn = {2041-1723}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/*genetics ; Case-Control Studies ; Cell Differentiation ; DNA Methylation/*genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Keratinocytes ; Keratosis, Actinic/*genetics ; Male ; Middle Aged ; Skin Neoplasms/*genetics ; Young Adult ; }, abstract = {Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and usually progresses from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain partially understood. Here, we use Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status in healthy, AK and cSCC epidermis samples. Importantly, we show that AK methylation patterns already display classical features of cancer methylomes and are highly similar to cSCC profiles. Further analysis identifies typical features of stem cell methylomes, such as reduced DNA methylation age, non-CpG methylation, and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature is detected only in half of the samples, while the other half shows patterns more closely related to healthy epidermis. These findings suggest the existence of two subclasses of AK and cSCC emerging from distinct keratinocyte differentiation stages.}, }
@article {pmid29383489, year = {2018}, author = {Yew, CW and Lu, D and Deng, L and Wong, LP and Ong, RT and Lu, Y and Wang, X and Yunus, Y and Aghakhanian, F and Mokhtar, SS and Hoque, MZ and Voo, CL and Abdul Rahman, T and Bhak, J and Phipps, ME and Xu, S and Teo, YY and Kumar, SV and Hoh, BP}, title = {Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia.}, journal = {Human genetics}, volume = {137}, number = {2}, pages = {161-173}, doi = {10.1007/s00439-018-1869-0}, pmid = {29383489}, issn = {1432-1203}, support = {100-RM/BIOTEK 16/6/2 B (1/2011)//Kementerian Sains, Teknologi dan Inovasi (MY)/ ; [100-RMI/GOV 16/6/2 (19/2011]//Kementerian Sains, Teknologi dan Inovasi (MY)/ ; 100-RM/BIOTEK 16/6/2 B (1/2011)//Kementerian Sains, Teknologi dan Inovasi (MY)/ ; 100-RM/BIOTEK 16/6/2 B (1/2011)//Kementerian Sains, Teknologi dan Inovasi (MY)/ ; FRGS/1/2015/ST03/UCSI/01/1//Ministry of Higher Education, Malaysia (MY)/ ; NRF-RF-2010-05//National Foundation for Cancer Research (US)/ ; NRF-RF-2010-05//National Foundation for Cancer Research (US)/ ; NRF-RF-2010-05//National Research Foundation Singapore (SG)/ ; 91331204//National Natural Science Foundation of China (CN)/ ; 31525014//National Natural Science Foundation of China (CN)/ ; 91731303//National Natural Science Foundation of China (CN)/ ; 31771388//National Natural Science Foundation of China (CN)/ ; 31501011//National Natural Science Foundation of China (CN)/ ; 31711530221//National Institutes of Natural Sciences (JP)/ ; 10040231//Industry Strategic Development Program/ ; (1.150014.01)//Ulsan National Institute of Science and Technology (KR)/ ; }, abstract = {Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.}, }
@article {pmid29320204, year = {2018}, author = {Shipilovskikh, SA and Vaganov, VY and Denisova, EI and Rubtsov, AE and Malkov, AV}, title = {Dehydration of Amides to Nitriles under Conditions of a Catalytic Appel Reaction.}, journal = {Organic letters}, volume = {20}, number = {3}, pages = {728-731}, doi = {10.1021/acs.orglett.7b03862}, pmid = {29320204}, issn = {1523-7052}, abstract = {A highly expedient protocol for a catalytic Appel-type dehydration of amides to nitriles has been developed that employs oxalyl chloride and triethylamine along with triphenylphosphine oxide as a catalyst. The reactions are usually complete in less than 10 min with only a 1 mol % catalyst loading. The reaction scope includes aromatic, heteroaromatic, and aliphatic amides, including derivatives of α-hydroxy and α-amino acids.}, }
@article {pmid29246791, year = {2018}, author = {Belousov, AB and Nishimune, H and Denisova, JV and Fontes, JD}, title = {A potential role for neuronal connexin 36 in the pathogenesis of amyotrophic lateral sclerosis.}, journal = {Neuroscience letters}, volume = {666}, number = {}, pages = {1-4}, doi = {10.1016/j.neulet.2017.12.027}, pmid = {29246791}, issn = {1872-7972}, support = {P30 AG035982/AG/NIA NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; R01 NS078214/NS/NINDS NIH HHS/United States ; UL1 TR000001/TR/NCATS NIH HHS/United States ; }, abstract = {Neuronal gap junctional protein connexin 36 (Cx36) contributes to neuronal death following a range of acute brain insults such as ischemia, traumatic brain injury and epilepsy. Whether Cx36 contributes to neuronal death and pathological outcomes in chronic neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), is not known. We show here that the expression of Cx36 is significantly decreased in lumbar segments of the spinal cord of both human ALS subjects and SOD1G93A mice as compared to healthy human and wild-type mouse controls, respectively. In purified neuronal cultures prepared from the spinal cord of wild-type mice, knockdown of Cx36 reduces neuronal death caused by overexpression of the mutant human SOD1-G93A protein. Taken together, these data suggest a possible contribution of Cx36 to ALS pathogenesis. A perspective for the use of blockers of Cx36 gap junction channels for ALS therapy is discussed.}, }
@article {pmid29215085, year = {2018}, author = {Derenko, M and Denisova, G and Malyarchuk, B and Dambueva, I and Bazarov, B}, title = {Mitogenomic diversity and differentiation of the Buryats.}, journal = {Journal of human genetics}, volume = {63}, number = {1}, pages = {71-81}, doi = {10.1038/s10038-017-0370-2}, pmid = {29215085}, issn = {1435-232X}, abstract = {In this paper we present a results of first comprehensive study of the complete mitogenomes in the Buryats with regard to their belonging to the main regional (eastern and western Buryats); tribal (Khori, Ekhirid, Bulagad, and Khongodor), and ethno-territorial (Aginsk, Alar, Balagansk, Barguzin, Ida, Khorinsk, Kuda, Selenga, Verkholensk, Olkhon, Tunka, and Shenehen Buryats) groups. The analysis of molecular variation performed using regional, tribal, and ethno-territorial divisions of the Buryats showed lack of genetic differentiation at all levels. Nonetheless, the complete mitogenome analysis revealed a very high level of genetic diversity in the Buryats which is the highest among Siberian populations and comparable to that in populations of eastern and western Asia. The AMOVA and MDS analyses results imply to a strong genetic similarity between the Buryats and eastern Asian populations of Chinese and Japanese, suggesting their origin on the basis of common maternal ancestry components. Several new Buryat-specific branches of haplogroup G (G2a2a, G2a1i, G2a5a) display signals of dispersals dating to 2.6-6.6 kya with a possible origin in eastern Asia, thus testifying Bronze Age and Neolithic arrival of ancestral eastern Asian component to the South Siberia region.}, }
@article {pmid29175608, year = {2018}, author = {Walter Costa, MB and Höner Zu Siederdissen, C and Tulpan, D and Stadler, PF and Nowick, K}, title = {Temporal ordering of substitutions in RNA evolution: Uncovering the structural evolution of the Human Accelerated Region 1.}, journal = {Journal of theoretical biology}, volume = {438}, number = {}, pages = {143-150}, doi = {10.1016/j.jtbi.2017.11.015}, pmid = {29175608}, issn = {1095-8541}, abstract = {The Human Accelerated Region 1 (HAR1) is the most rapidly evolving region in the human genome. It is part of two overlapping long non-coding RNAs, has a length of only 118 nucleotides and features 18 human specific changes compared to an ancestral sequence that is extremely well conserved across non-human primates. The human HAR1 forms a stable secondary structure that is strikingly different from the one in chimpanzee as well as other closely related species, again emphasizing its human-specific evolutionary history. This suggests that positive selection has acted to stabilize human-specific features in the ensemble of HAR1 secondary structures. To investigate the evolutionary history of the human HAR1 structure, we developed a computational model that evaluates the relative likelihood of evolutionary trajectories as a probabilistic version of a Hamiltonian path problem. The model predicts that the most likely last step in turning the ancestral primate HAR1 into the human HAR1 was exactly the substitution that distinguishes the modern human HAR1 sequence from that of Denisovan, an archaic human, providing independent support for our model. The MutationOrder software is available for download and can be applied to other instances of RNA structure evolution.}, }
@article {pmid29171471, year = {2017}, author = {Kovalkova, NA and Ragino, YI and Travnikova, NY and Denisova, DV and Shcherbakova, LV and Voevoda, MI}, title = {[Associations between metabolic syndrome and reduced lung function in young people].}, journal = {Terapevticheskii arkhiv}, volume = {89}, number = {10}, pages = {54-61}, doi = {10.17116/terarkh2017891054-61}, pmid = {29171471}, issn = {0040-3660}, mesh = {Adult ; Blood Glucose/analysis ; *Blood Pressure Determination/methods/statistics & numerical data ; Body Mass Index ; Cardiovascular Diseases/*epidemiology ; Cholesterol/blood ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Female ; Humans ; Male ; *Metabolic Syndrome/blood/diagnosis/epidemiology/physiopathology ; Prevalence ; Respiratory Function Tests/methods/statistics & numerical data ; *Respiratory Insufficiency/diagnosis/epidemiology/physiopathology ; Risk Factors ; Siberia/epidemiology ; Statistics as Topic ; Triglycerides/blood ; *Waist Circumference ; }, abstract = {AIM: To reveal possible associations between metabolic syndrome (MS) and reduced lung function.

SUBJECTS AND METHODS: In 2013-016, a cross-sectional survey was conducted in 908 Novosibirsk dwellers, which included spirometry to evaluate external respiratory function (ERF). For the detection of MS, the investigators used the 2009 All-Russian Research Society of Cardiologists criteria: waist circumference (WC) > 80 cm for women and >94 cm for men in combination with two of the following criteria: blood pressure (BP) ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, high-density lipoproteins (HDL) cholesterol <1.0 mmol/l for men and <1.2 mmol/l for women, low-density lipoprotein (LDL) cholesterol >3.0 mmol/l, and glucose ≥6.1 mmol/l.

RESULTS: The mean values of WC were significantly greater with a forced expiratory volume in one second (FEV1) <80% than those with a FEV1 of ≥80% in both men (p=0.002) and women (p=0.050); in women, the mean values of WS were higher than those with a FEV1/forced vital capacity (FVC) <70% than those with a FEV1/FVC of ≥70% (p=0.047); the mean systolic and diastolic BP levels were significantly more with reductions in FEV1 and FVC, and the level of HDL cholesterol was significantly lower than that with a FEV1 of < 80% in men only. Significant correlations were found between FEV1 and all components of MS in men, between the majority of components of MS and FVC in men, between WC, BP, and FEV1/FVC in men and women, between plasma glucose levels and FEV1/FVC in women. Linear regression analysis revealed significant inverse correlations of FEV1 with TG, glucose, BP; those of FVC with TG, glucose; at the same time a positive association with HDL cholesterol in men, and only a negative correlation of FEV1/FVC with WC.

CONCLUSION: The revealed associations between MS and reduced lung function can most likely be explained by the greater prevalence of both MS and its components (hypertension, hypertriglyceridemia, hyperglycemia, LDL hypercholesterolemia) among Novosibirsk men. This is consistent with the assertion that the decline in ERF, particularly FEV1, may be a marker of future cardiovascular disease morbidity and mortality.}, }
@article {pmid29072654, year = {2017}, author = {Soldatsky, YL and Denisova, OA and Bulynko, SA}, title = {[The specific features of the past medical history and etiology of pharyngeal abscess in the children].}, journal = {Vestnik otorinolaringologii}, volume = {82}, number = {5}, pages = {12-14}, doi = {10.17116/otorino201782512-14}, pmid = {29072654}, issn = {0042-4668}, mesh = {Adolescent ; Anti-Bacterial Agents/*therapeutic use ; Child ; Female ; Humans ; Male ; Medical History Taking ; Needs Assessment ; *Patient Care Management/methods/organization & administration/standards ; *Peritonsillar Abscess/diagnosis/etiology/prevention & control ; *Retropharyngeal Abscess/diagnosis/etiology/prevention & control ; Risk Factors ; Russia/epidemiology ; *Streptococcal Infections/complications/diagnosis/drug therapy/epidemiology ; *Streptococcus pyogenes/isolation & purification/pathogenicity ; Tonsillectomy/*methods ; *Tonsillitis/complications/diagnosis/epidemiology/therapy ; }, abstract = {The present study was undertaken for the purpose of elucidating the specific features of the past medical history and the etiological factors responsible for the development of tonsillogenic pharyngeal abscesses in the children. We performed the retrospective analysis of the medical histories of 291 children presenting with this condition who had been admitted for the treatment to the ENT Department of the Morozovskzya City Children's Clinical Hospital during the period from January till December 2015. The study has demonstrated the following most common shortcomings of the outpatient treatment of the patients suffering from chronic tonsillitis at the stage preceding formation of paratonsillar abscess: inadequate antibacterial therapy of acute chronic tonsillitis or its exacerbation and limited indications for tonsillectomy at the level of the outpatient treatment. The leading role in the etiology of tonsillogenic pharyngeal abscesses in the children is played by beta-hemolytic Streptococcus of group A. It is concluded that the medical history suggesting past paratonsillar abscess is the absolute indication for the subsequent tonsillectomy in the children of any age.}, }
@article {pmid29053564, year = {2018}, author = {Yazdanyar, A and Rizzuti, AE and Mechel, E and Denisova, K and Lazzaro, DR}, title = {Gout Keratitis: A Case of Peripheral Ulcerative Keratitis Secondary to Gout With a Review of the Literature.}, journal = {Cornea}, volume = {37}, number = {3}, pages = {379-381}, doi = {10.1097/ICO.0000000000001415}, pmid = {29053564}, issn = {1536-4798}, mesh = {Adult ; Corneal Stroma/pathology ; Corneal Ulcer/*etiology/metabolism/pathology ; Gout/*complications ; Humans ; Male ; Uric Acid/metabolism ; }, abstract = {PURPOSE: To report a case of peripheral ulcerative keratitis secondary to gout.

METHODS: A 41-year-old man with a history of severe gout disease presented with pain and redness of the right eye. Physical examination revealed 2 areas of peripheral corneal thinning with overlying epithelial defects. Adjacent to these areas, reflective crystals were identified in the corneal stroma. Anterior segment optical coherence tomography demonstrated stromal corneal deposits.

RESULTS: Systemic workup was negative aside from an elevated serum uric acid level. The patient was administered oral prednisone, allopurinol, and colchicine. At his 2-month follow-up visit, the patient was asymptomatic and his corneal thinning had significantly improved.

CONCLUSIONS: Gout is the most common type of inflammatory arthritis in adults with rising incidence and prevalence. Ocular findings in gout are common, but patients are usually asymptomatic. Monosodium urate crystal deposition has been reported to occur in various parts of the eye, with and without ocular inflammation. Crystal deposition in the cornea is extremely rare and may be a cause of peripheral ulcerative keratitis.}, }
@article {pmid28989973, year = {2017}, author = {Vashee, S and Stockwell, TB and Alperovich, N and Denisova, EA and Gibson, DG and Cady, KC and Miller, K and Kannan, K and Malouli, D and Crawford, LB and Voorhies, AA and Bruening, E and Caposio, P and Früh, K}, title = {Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination.}, journal = {mSphere}, volume = {2}, number = {5}, pages = {}, doi = {10.1128/mSphereDirect.00331-17}, pmid = {28989973}, issn = {2379-5042}, support = {R41 AI106090/AI/NIAID NIH HHS/United States ; }, abstract = {Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full-length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes.}, }
@article {pmid28980560, year = {2017}, author = {Saakyan, SV and Katargina, LA and Krichevskaya, GI and Myakoshina, EB and Denisova, EV}, title = {[Specific immunoglobulins G and M in blood serum in retinoblastoma and 'pseudoretinoblastoma'].}, journal = {Vestnik oftalmologii}, volume = {133}, number = {4}, pages = {12-16}, doi = {10.17116/oftalma2017133412-16}, pmid = {28980560}, issn = {0042-465X}, mesh = {Antibodies, Bacterial/*blood ; Antibodies, Viral/*blood ; Child, Preschool ; *Cytomegalovirus Retinitis/diagnosis/etiology ; Diagnosis, Differential ; Eye Abnormalities/*diagnosis ; Female ; Humans ; Immunoglobulin G/*blood ; Immunoglobulin M/*blood ; Infant ; Infant, Newborn ; Male ; Neonatal Screening ; Pregnancy ; Prenatal Exposure Delayed Effects/*diagnosis/microbiology ; Retina/abnormalities/microbiology ; *Retinal Neoplasms/diagnosis/immunology/microbiology/pathology ; *Retinoblastoma/diagnosis/immunology/microbiology/pathology ; }, abstract = {Perinatal inflammatory retinal diseases and intrauterine retinal maldevelopments are mistaken for retinoblastoma as often as in 8-16% of cases.

AIM: To analyze the infectious status in children with retinoblastoma and pseudoretinoblastoma at different ages.

MATERIAL AND METHODS: A total of 47 retinoblastoma suspects aged 4-69 months were enrolled. Pseudoretinoblastoma (inflammatory retinal diseases and intrauterine maldevelopments of the retina) was detected in 14 children (group 1), retinoblastoma - in 33 children (group 2). In each group, two subgroups were identified: 'a' - children under 12 months of age (1a - 5 patients, 2a - 10 patients) and 'b'- children over 12 months of age (1b - 9 patients, 2b - 23 patients). Their blood sera were examined for antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, toxoplasma, toxocara, chlamydia, and mycoplasma (enzyme-linked immunosorbent assay).

RESULTS: According to serological screening, all patients from group 1a (children under 12 months of age with pseudoretinoblastoma), in contrast to other groups, were infected perinatally with cytomegalovirus infection. All 47 patients were seronegative to toxoplasma. Toxocara infection was identified in children over 12 months of age: in 3 out of 9 patients with pseudoretinoblastoma and in 2 out of 23 patients with retinoblastoma (p>0.05). Markers of Epstein-Barr viral activity were detected only in 3 retinoblastoma children over 12 months of age.

CONCLUSION: The results suggest that cytomegalovirus infection plays the leading role in the development of perinatal eye pathology, which, in infants, is clinically similar to retinoblastoma. In children over 12 months of age we found no serological signs that could be regarded as specific of either retinoblastoma, or pseudoretinoblastoma. The only thing worth paying attention to is the activation of Epstein-Barr virus infection in children over 12 months of age with retinoblastoma.}, }
@article {pmid28950836, year = {2017}, author = {Xu, D and Jaber, Y and Pavlidis, P and Gokcumen, O}, title = {VCFtoTree: a user-friendly tool to construct locus-specific alignments and phylogenies from thousands of anthropologically relevant genome sequences.}, journal = {BMC bioinformatics}, volume = {18}, number = {1}, pages = {426}, doi = {10.1186/s12859-017-1844-0}, pmid = {28950836}, issn = {1471-2105}, mesh = {Algorithms ; Animals ; Base Sequence ; *Genetic Loci ; *Genome, Human ; Humans ; INDEL Mutation/genetics ; *Phylogeny ; Primates ; Sequence Alignment/*methods ; Sequence Analysis, DNA ; *Software ; User-Computer Interface ; }, abstract = {BACKGROUND: Constructing alignments and phylogenies for a given locus from large genome sequencing studies with relevant outgroups allow novel evolutionary and anthropological insights. However, no user-friendly tool has been developed to integrate thousands of recently available and anthropologically relevant genome sequences to construct complete sequence alignments and phylogenies.

RESULTS: Here, we provide VCFtoTree, a user friendly tool with a graphical user interface that directly accesses online databases to download, parse and analyze genome variation data for regions of interest. Our pipeline combines popular sequence datasets and tree building algorithms with custom data parsing to generate accurate alignments and phylogenies using all the individuals from the 1000 Genomes Project, Neanderthal and Denisovan genomes, as well as reference genomes of Chimpanzee and Rhesus Macaque. It can also be applied to other phased human genomes, as well as genomes from other species. The output of our pipeline includes an alignment in FASTA format and a tree file in newick format.

CONCLUSION: VCFtoTree fulfills the increasing demand for constructing alignments and phylogenies for a given loci from thousands of available genomes. Our software provides a user friendly interface for a wider audience without prerequisite knowledge in programming. VCFtoTree can be accessed from https://github.com/duoduoo/VCFtoTree_3.0.0 .}, }
@article {pmid28902892, year = {2017}, author = {Zanolli, C and Hourset, M and Esclassan, R and Mollereau, C}, title = {Neanderthal and Denisova tooth protein variants in present-day humans.}, journal = {PloS one}, volume = {12}, number = {9}, pages = {e0183802}, doi = {10.1371/journal.pone.0183802}, pmid = {28902892}, issn = {1932-6203}, mesh = {Animals ; Dental Enamel/anatomy & histology/metabolism ; Dental Enamel Proteins/*genetics/metabolism ; Fossils ; Gene Frequency ; Genome, Human ; Geography ; *Hominidae/genetics/metabolism ; Humans ; *Neanderthals/genetics/metabolism ; Organ Size ; Phylogeny ; *Polymorphism, Genetic ; Selection, Genetic ; Sequence Homology, Amino Acid ; Tooth/anatomy & histology/chemistry/*metabolism ; }, abstract = {Environment parameters, diet and genetic factors interact to shape tooth morphostructure. In the human lineage, archaic and modern hominins show differences in dental traits, including enamel thickness, but variability also exists among living populations. Several polymorphisms, in particular in the non-collagenous extracellular matrix proteins of the tooth hard tissues, like enamelin, are involved in dental structure variation and defects and may be associated with dental disorders or susceptibility to caries. To gain insights into the relationships between tooth protein polymorphisms and dental structural morphology and defects, we searched for non-synonymous polymorphisms in tooth proteins from Neanderthal and Denisova hominins. The objective was to identify archaic-specific missense variants that may explain the dental morphostructural variability between extinct and modern humans, and to explore their putative impact on present-day dental phenotypes. Thirteen non-collagenous extracellular matrix proteins specific to hard dental tissues have been selected, searched in the publicly available sequence databases of Neanderthal and Denisova individuals and compared with modern human genome data. A total of 16 non-synonymous polymorphisms were identified in 6 proteins (ameloblastin, amelotin, cementum protein 1, dentin matrix acidic phosphoprotein 1, enamelin and matrix Gla protein). Most of them are encoded by dentin and enamel genes located on chromosome 4, previously reported to show signs of archaic introgression within Africa. Among the variants shared with modern humans, two are ancestral (common with apes) and one is the derived enamelin major variant, T648I (rs7671281), associated with a thinner enamel and specific to the Homo lineage. All the others are specific to Neanderthals and Denisova, and are found at a very low frequency in modern Africans or East and South Asians, suggesting that they may be related to particular dental traits or disease susceptibility in these populations. This modern regional distribution of archaic dental polymorphisms may reflect persistence of archaic variants in some populations and may contribute in part to the geographic dental variations described in modern humans.}, }
@article {pmid28900155, year = {2017}, author = {Denisova, K and Zhao, G}, title = {Inflexible neurobiological signatures precede atypical development in infants at high risk for autism.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {11285}, doi = {10.1038/s41598-017-09028-0}, pmid = {28900155}, issn = {2045-2322}, abstract = {Variability in neurobiological signatures is ubiquitous in early life but the link to adverse developmental milestones in humans is unknown. We examined how levels of signal and noise in movement signatures during the 1st year of life constrain early development in 71 healthy typically developing infants, either at High or Low familial Risk (HR or LR, respectively) for developing Autism Spectrum Disorders (ASD). Delays in early learning developmental trajectories in HR infants (validated in an analysis of 1,445 infants from representative inf﻿ant-sibling studies) were predicted by worse stochastic patterns in their spontaneous head movements as early as 1-2 months after birth, relative to HR infants who showed more rapid developmental progress, as well as relative to all LR infants. While LR 1-2 mo-old infants' movements were significantly different during a language listening task compared to during sleep, HR infants' movements were more similar during both conditions, a striking lack of diversity that reveals context-inflexible experience of ambient information. Contrary to expectation, it is not the level of variability per se that is particularly detrimental in early life. Rather, inflexible sensorimotor systems and/or atypical transition between behavioral states may interfere with the establishment of capacity to extract structure and important cues from sensory input at birth, preceding and contributing to an atypical brain developmental trajectory in toddlerhood.}, }
@article {pmid28855259, year = {2017}, author = {Gardner, EJ and Lam, VK and Harris, DN and Chuang, NT and Scott, EC and Pittard, WS and Mills, RE and , and Devine, SE}, title = {The Mobile Element Locator Tool (MELT): population-scale mobile element discovery and biology.}, journal = {Genome research}, volume = {27}, number = {11}, pages = {1916-1929}, doi = {10.1101/gr.218032.116}, pmid = {28855259}, issn = {1549-5469}, support = {R01 HG002898/HG/NHGRI NIH HHS/United States ; R01 HG006849/HG/NHGRI NIH HHS/United States ; R01 GM059290/GM/NIGMS NIH HHS/United States ; R01 CA166661/CA/NCI NIH HHS/United States ; F31 HG009223/HG/NHGRI NIH HHS/United States ; T32 DK067872/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Computational Biology/*methods ; *DNA Transposable Elements ; Databases, Genetic ; Evolution, Molecular ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Neanderthals/*genetics ; Pan troglodytes/*genetics ; Polymorphism, Single Nucleotide ; Software ; Whole Genome Sequencing/methods ; }, abstract = {Mobile element insertions (MEIs) represent ∼25% of all structural variants in human genomes. Moreover, when they disrupt genes, MEIs can influence human traits and diseases. Therefore, MEIs should be fully discovered along with other forms of genetic variation in whole genome sequencing (WGS) projects involving population genetics, human diseases, and clinical genomics. Here, we describe the Mobile Element Locator Tool (MELT), which was developed as part of the 1000 Genomes Project to perform MEI discovery on a population scale. Using both Illumina WGS data and simulations, we demonstrate that MELT outperforms existing MEI discovery tools in terms of speed, scalability, specificity, and sensitivity, while also detecting a broader spectrum of MEI-associated features. Several run modes were developed to perform MEI discovery on local and cloud systems. In addition to using MELT to discover MEIs in modern humans as part of the 1000 Genomes Project, we also used it to discover MEIs in chimpanzees and ancient (Neanderthal and Denisovan) hominids. We detected diverse patterns of MEI stratification across these populations that likely were caused by (1) diverse rates of MEI production from source elements, (2) diverse patterns of MEI inheritance, and (3) the introgression of ancient MEIs into modern human genomes. Overall, our study provides the most comprehensive map of MEIs to date spanning chimpanzees, ancient hominids, and modern humans and reveals new aspects of MEI biology in these lineages. We also demonstrate that MELT is a robust platform for MEI discovery and analysis in a variety of experimental settings.}, }
@article {pmid28854687, year = {2017}, author = {Jinam, TA and Phipps, ME and Aghakhanian, F and Majumder, PP and Datar, F and Stoneking, M and Sawai, H and Nishida, N and Tokunaga, K and Kawamura, S and Omoto, K and Saitou, N}, title = {Discerning the Origins of the Negritos, First Sundaland People: Deep Divergence and Archaic Admixture.}, journal = {Genome biology and evolution}, volume = {9}, number = {8}, pages = {2013-2022}, doi = {10.1093/gbe/evx118}, pmid = {28854687}, issn = {1759-6653}, mesh = {Asian Continental Ancestry Group/genetics ; *Genetics, Population ; *Genome, Human ; Genome-Wide Association Study ; Humans ; Malaysia ; Philippines ; *Phylogeny ; *Polymorphism, Single Nucleotide ; }, abstract = {Human presence in Southeast Asia dates back to at least 40,000 years ago, when the current islands formed a continental shelf called Sundaland. In the Philippine Islands, Peninsular Malaysia, and Andaman Islands, there exist indigenous groups collectively called Negritos whose ancestry can be traced to the "First Sundaland People." To understand the relationship between these Negrito groups and their demographic histories, we generated genome-wide single nucleotide polymorphism data in the Philippine Negritos and compared them with existing data from other populations. Phylogenetic tree analyses show that Negritos are basal to other East and Southeast Asians, and that they diverged from West Eurasians at least 38,000 years ago. We also found relatively high traces of Denisovan admixture in the Philippine Negritos, but not in the Malaysian and Andamanese groups, suggesting independent introgression and/or parallel losses involving Denisovan introgressed regions. Shared genetic loci between all three Negrito groups could be related to skin pigmentation, height, facial morphology and malarial resistance. These results show the unique status of Negrito groups as descended from the First Sundaland People.}, }
@article {pmid28854627, year = {2017}, author = {Sharbrough, J and Havird, JC and Noe, GR and Warren, JM and Sloan, DB}, title = {The Mitonuclear Dimension of Neanderthal and Denisovan Ancestry in Modern Human Genomes.}, journal = {Genome biology and evolution}, volume = {9}, number = {6}, pages = {1567-1581}, doi = {10.1093/gbe/evx114}, pmid = {28854627}, issn = {1759-6653}, mesh = {Alleles ; Animals ; Cell Nucleus/chemistry/*genetics ; DNA, Mitochondrial/chemistry/*genetics ; *Evolution, Molecular ; Gene Flow ; *Genome, Human ; Hominidae/classification/*genetics ; Humans ; Neanderthals/classification/*genetics ; Nucleic Acid Conformation ; Polymorphism, Genetic ; Reproductive Isolation ; }, abstract = {Some human populations interbred with Neanderthals and Denisovans, resulting in substantial contributions to modern-human genomes. Therefore, it is now possible to use genomic data to investigate mechanisms that shaped historical gene flow between humans and our closest hominin relatives. More generally, in eukaryotes, mitonuclear interactions have been argued to play a disproportionate role in generating reproductive isolation. There is no evidence of mtDNA introgression into modern human populations, which means that all introgressed nuclear alleles from archaic hominins must function on a modern-human mitochondrial background. Therefore, mitonuclear interactions are also potentially relevant to hominin evolution. We performed a detailed accounting of mtDNA divergence among hominin lineages and used population-genomic data to test the hypothesis that mitonuclear incompatibilities have preferentially restricted the introgression of nuclear genes with mitochondrial functions. We found a small but significant underrepresentation of introgressed Neanderthal alleles at such nuclear loci. Structural analyses of mitochondrial enzyme complexes revealed that these effects are unlikely to be mediated by physically interacting sites in mitochondrial and nuclear gene products. We did not detect any underrepresentation of introgressed Denisovan alleles at mitochondrial-targeted loci, but this may reflect reduced power because locus-specific estimates of Denisovan introgression are more conservative. Overall, we conclude that genes involved in mitochondrial function may have been subject to distinct selection pressures during the history of introgression from archaic hominins but that mitonuclear incompatibilities have had, at most, a small role in shaping genome-wide introgression patterns, perhaps because of limited functional divergence in mtDNA and interacting nuclear genes.}, }
@article {pmid28784789, year = {2017}, author = {Rogers, AR and Bohlender, RJ and Huff, CD}, title = {Early history of Neanderthals and Denisovans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {37}, pages = {9859-9863}, doi = {10.1073/pnas.1706426114}, pmid = {28784789}, issn = {1091-6490}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R25 CA057730/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Evolution, Molecular ; Fossils ; Gene Flow/*genetics ; Genome, Human/genetics ; Hominidae/*classification/*genetics ; Humans ; Neanderthals/classification/*genetics ; *Pedigree ; Phylogeny ; }, abstract = {Extensive DNA sequence data have made it possible to reconstruct human evolutionary history in unprecedented detail. We introduce a method to study the past several hundred thousand years. Our results show that (i) the Neanderthal-Denisovan lineage declined to a small size just after separating from the modern lineage, (ii) Neanderthals and Denisovans separated soon thereafter, and (iii) the subsequent Neanderthal population was large and deeply subdivided. They also (iv) support previous estimates of gene flow from Neanderthals into modern Eurasians. These results suggest an archaic human diaspora early in the Middle Pleistocene.}, }
@article {pmid28695206, year = {2017}, author = {Slon, V and Viola, B and Renaud, G and Gansauge, MT and Benazzi, S and Sawyer, S and Hublin, JJ and Shunkov, MV and Derevianko, AP and Kelso, J and Prüfer, K and Meyer, M and Pääbo, S}, title = {A fourth Denisovan individual.}, journal = {Science advances}, volume = {3}, number = {7}, pages = {e1700186}, doi = {10.1126/sciadv.1700186}, pmid = {28695206}, issn = {2375-2548}, abstract = {The presence of Neandertals in Europe and Western Eurasia before the arrival of anatomically modern humans is well supported by archaeological and paleontological data. In contrast, fossil evidence for Denisovans, a sister group of Neandertals recently identified on the basis of DNA sequences, is limited to three specimens, all of which originate from Denisova Cave in the Altai Mountains (Siberia, Russia). We report the retrieval of DNA from a deciduous lower second molar (Denisova 2), discovered in a deep stratigraphic layer in Denisova Cave, and show that this tooth comes from a female Denisovan individual. On the basis of the number of "missing substitutions" in the mitochondrial DNA determined from the specimen, we find that Denisova 2 is substantially older than two of the other Denisovans, reinforcing the view that Denisovans were likely to have been present in the vicinity of Denisova Cave over an extended time period. We show that the level of nuclear DNA sequence diversity found among Denisovans is within the lower range of that of present-day human populations.}, }
@article {pmid28669760, year = {2017}, author = {Margaryan, A and Derenko, M and Hovhannisyan, H and Malyarchuk, B and Heller, R and Khachatryan, Z and Avetisyan, P and Badalyan, R and Bobokhyan, A and Melikyan, V and Sargsyan, G and Piliposyan, A and Simonyan, H and Mkrtchyan, R and Denisova, G and Yepiskoposyan, L and Willerslev, E and Allentoft, ME}, title = {Eight Millennia of Matrilineal Genetic Continuity in the South Caucasus.}, journal = {Current biology : CB}, volume = {27}, number = {13}, pages = {2023-2028.e7}, doi = {10.1016/j.cub.2017.05.087}, pmid = {28669760}, issn = {1879-0445}, abstract = {The South Caucasus, situated between the Black and Caspian Seas, geographically links Europe with the Near East and has served as a crossroad for human migrations for many millennia [1-7]. Despite a vast archaeological record showing distinct cultural turnovers, the demographic events that shaped the human populations of this region is not known [8, 9]. To shed light on the maternal genetic history of the region, we analyzed the complete mitochondrial genomes of 52 ancient skeletons from present-day Armenia and Artsakh spanning 7,800 years and combined this dataset with 206 mitochondrial genomes of modern Armenians. We also included previously published data of seven neighboring populations (n = 482). Coalescence-based analyses suggest that the population size in this region rapidly increased after the Last Glacial Maximum ca. 18 kya. We find that the lowest genetic distance in this dataset is between modern Armenians and the ancient individuals, as also reflected in both network analyses and discriminant analysis of principal components. We used approximate Bayesian computation to test five different demographic scenarios explaining the formation of the modern Armenian gene pool. Despite well documented cultural shifts in the South Caucasus across this time period, our results strongly favor a genetic continuity model in the maternal gene pool. This has implications for interpreting prehistoric migration dynamics and cultural shifts in this part of the world.}, }
@article {pmid28655834, year = {2017}, author = {Easton, JD and Aunes, M and Albers, GW and Amarenco, P and Bokelund-Singh, S and Denison, H and Evans, SR and Held, P and Jahreskog, M and Jonasson, J and Minematsu, K and Molina, CA and Wang, Y and Wong, KSL and Johnston, SC and , }, title = {Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).}, journal = {Circulation}, volume = {136}, number = {10}, pages = {907-916}, doi = {10.1161/CIRCULATIONAHA.117.028566}, pmid = {28655834}, issn = {1524-4539}, mesh = {Adenosine/administration & dosage/adverse effects/*analogs & derivatives ; Aged ; Aspirin/administration & dosage/*adverse effects ; Female ; Hemorrhage/*chemically induced ; Humans ; Ischemic Attack, Transient/*complications/drug therapy ; Male ; Purinergic P2Y Receptor Antagonists/administration & dosage/*adverse effects ; Risk ; Stroke/*complications/drug therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH).

METHODS: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population.

RESULTS: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor.

CONCLUSIONS: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs.

METHODS: A total of 197 juvenile patients were enrolled in this study. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the Wallace criteria, and the Juvenile Arthritis Disease Activity Score 71 (JADAS-71). Univariate and multivariate logistic regression analyses were performed to identify potential baseline factors associated with treatment response in different JIA categories.

RESULTS: One year after treatment initiation, 179 (90.9%) patients achieved ACRPedi30; 177 (89.8%) patients achieved ACRPedi50; 168 (85.3%) patients achieved ACRPedi70; and 135 (68.5%) patients achieved ACRPedi90 response. A total of 132 (67.0%) and 92 (46.7%) patients achieved inactive disease according to the Wallace criteria and the JADAS-71 cut-off point, respectively. Excellent response (achieving ACRPedi90 and clinically inactive disease according both to the Wallace criteria and the JADAS71 cut-off point) was associated with persistent oligoarticular JIA category, shorter disease duration before the start of etanercept, a lower number of DMARDs used before the introduction of etanercept, a lower number of joints with limited motion, and lower C-reactive protein at baseline. Poor response (failure to achieve ACR 70 or active disease according to both the Wallace criteria and JADAS71 even when ACR 70 was achieved) was associated with the polyarticular or enthesitis-related JIA categories, higher disease duration before the start of etanercept, and older age at disease onset.

CONCLUSION: Almost half (45.7%) of the patients who initiated etanercept treatment achieved an excellent response (inactive disease and ACRPedi90) after 1 year. What may be novel is our finding that the response to etanercept therapy was strongly associated with the JIA category. The response to etanercept therapy was also associated with the disease duration before the start of etanercept treatment.}, }
@article {pmid28572766, year = {2017}, author = {Guo, S and Lai, C and Wu, C and Cen, G and , }, title = {Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images.}, journal = {Frontiers in aging neuroscience}, volume = {9}, number = {}, pages = {146}, doi = {10.3389/fnagi.2017.00146}, pmid = {28572766}, issn = {1663-4365}, support = {K23 NS083711/NS/NINDS NIH HHS/United States ; P30 AG010129/AG/NIA NIH HHS/United States ; P50 AG005142/AG/NIA NIH HHS/United States ; }, abstract = {Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI-cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI-NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI-NC comparison. The best performances obtained by the SVM classifier using the essential features were 5-40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.}, }
@article {pmid28514400, year = {2017}, author = {Denisova, OA and Livzan, MA and Denisov, AP}, title = {[Comparative characteristics of patients with gastroesophageal reflux disease in the age aspect].}, journal = {Terapevticheskii arkhiv}, volume = {89}, number = {4}, pages = {53-56}, pmid = {28514400}, issn = {0040-3660}, abstract = {AIM: To compare the characteristics of patients with gastroesophageal reflux disease (GERD) by age groups, a wide range of clinical signs, including life-of-quality (QOL) indicators, and instrumental findings.

SUBJECTS AND METHODS: A total of 110 patients aged 18 to 86 years with GERD were examined in accordance with the standard protocol. Two groups with equal numbers of patents were formed. A study group included elderly and senile patients and a control group consisted of young and adult ones.

RESULTS: The elderly patients with GERD were observed to have a number of age-related clinical features and age-unrelated symptoms. The scores in the scales characterizing the physical health component and those in the general health and vital activity scales were markedly decreased in patients older than 60 years of age. No age-related statistically significant differences were found in the esophageal, gastric, and duodenal mucosae. Daily pH-metry in the elderly showed indirect evidence for esophageal hypomotor dyskinesia in the predominance of alkaline refluxes.

MATERIALS AND METHODS: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36 rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701). Additionally, APOE genotypes from 39 individuals were obtained from the literature. AMOVA, main effects, and gene-gene interaction tests were performed.

RESULTS: We observed differences in allele distribution patterns between agriculturalists and hunter-gatherers for some markers. For instance, between-groups component of genetic variance (FCT) for APOE rs429358 showed strong differences in allelic distributions between hunter-gatherers and agriculturalists (p = 0.00196). Gene-gene interaction analysis indicated that the APOE E4/CD36 TT and APOE E4/IGF2BP2 A carrier combinations occur at a higher frequency in hunter-gatherers, but this combination is not replicated in archaic (Neanderthal and Denisovan) and ancient (Anzick, Saqqaq, Ust-Ishim, Mal'ta) hunter-gatherer individuals.

DISCUSSION: A complex scenario explains the observed frequencies of the tested markers in hunter-gatherers. Different factors, such as pleotropic alleles, rainforest selective pressures, and population dynamics, may be collectively shaping the observed genetic patterns. We conclude that although TGH seems a plausible hypothesis to explain part of the data, other factors may be important in our tested populations.}, }
@article {pmid28450384, year = {2017}, author = {Slon, V and Hopfe, C and Weiß, CL and Mafessoni, F and de la Rasilla, M and Lalueza-Fox, C and Rosas, A and Soressi, M and Knul, MV and Miller, R and Stewart, JR and Derevianko, AP and Jacobs, Z and Li, B and Roberts, RG and Shunkov, MV and de Lumley, H and Perrenoud, C and Gušić, I and Kućan, Ž and Rudan, P and Aximu-Petri, A and Essel, E and Nagel, S and Nickel, B and Schmidt, A and Prüfer, K and Kelso, J and Burbano, HA and Pääbo, S and Meyer, M}, title = {Neandertal and Denisovan DNA from Pleistocene sediments.}, journal = {Science (New York, N.Y.)}, volume = {356}, number = {6338}, pages = {605-608}, doi = {10.1126/science.aam9695}, pmid = {28450384}, issn = {1095-9203}, mesh = {Animals ; Caves ; DNA, Ancient/analysis/*isolation & purification ; DNA, Mitochondrial/analysis/*isolation & purification ; Europe ; Fossils ; Geologic Sediments/chemistry ; Hominidae/*classification/*genetics ; Sequence Analysis, DNA ; }, abstract = {Although a rich record of Pleistocene human-associated archaeological assemblages exists, the scarcity of hominin fossils often impedes the understanding of which hominins occupied a site. Using targeted enrichment of mitochondrial DNA, we show that cave sediments represent a rich source of ancient mammalian DNA that often includes traces of hominin DNA, even at sites and in layers where no hominin remains have been discovered. By automation-assisted screening of numerous sediment samples, we detected Neandertal DNA in eight archaeological layers from four caves in Eurasia. In Denisova Cave, we retrieved Denisovan DNA in a Middle Pleistocene layer near the bottom of the stratigraphy. Our work opens the possibility of detecting the presence of hominin groups at sites and in areas where no skeletal remains are found.}, }
@article {pmid28448578, year = {2017}, author = {Hu, H and Petousi, N and Glusman, G and Yu, Y and Bohlender, R and Tashi, T and Downie, JM and Roach, JC and Cole, AM and Lorenzo, FR and Rogers, AR and Brunkow, ME and Cavalleri, G and Hood, L and Alpatty, SM and Prchal, JT and Jorde, LB and Robbins, PA and Simonson, TS and Huff, CD}, title = {Evolutionary history of Tibetans inferred from whole-genome sequencing.}, journal = {PLoS genetics}, volume = {13}, number = {4}, pages = {e1006675}, doi = {10.1371/journal.pgen.1006675}, pmid = {28448578}, issn = {1553-7404}, support = {R00 HL118215/HL/NHLBI NIH HHS/United States ; R35 GM118335/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Altitude ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cytochrome P-450 Enzyme System/genetics ; Female ; *Genome, Human ; Haplotypes ; High-Throughput Nucleotide Sequencing ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases/genetics ; Male ; Molecular Sequence Annotation ; Proteins/genetics ; Receptors, Calcitriol/genetics ; Selection, Genetic/*genetics ; Tibet ; }, abstract = {The indigenous people of the Tibetan Plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude. Recent studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high altitude-adaptation and originated in an archaic Denisovan-related population. We sequenced the whole-genomes of 27 Tibetans and conducted analyses to infer a detailed history of demography and natural selection of this population. We detected evidence of population structure between the ancestral Han and Tibetan subpopulations as early as 44 to 58 thousand years ago, but with high rates of gene flow until approximately 9 thousand years ago. The CMS test ranked EPAS1 and EGLN1 as the top two positive selection candidates, and in addition identified PTGIS, VDR, and KCTD12 as new candidate genes. The advantageous Tibetan EPAS1 haplotype shared many variants with the Denisovan genome, with an ancient gene tree divergence between the Tibetan and Denisovan haplotypes of about 1 million years ago. With the exception of EPAS1, we observed no evidence of positive selection on Denisovan-like haplotypes.}, }
@article {pmid28444387, year = {2017}, author = {Jégou, B and Sankararaman, S and Rolland, AD and Reich, D and Chalmel, F}, title = {Meiotic Genes Are Enriched in Regions of Reduced Archaic Ancestry.}, journal = {Molecular biology and evolution}, volume = {34}, number = {8}, pages = {1974-1980}, doi = {10.1093/molbev/msx141}, pmid = {28444387}, issn = {1537-1719}, support = {R00 GM111744/GM/NIGMS NIH HHS/United States ; R01 GM100233/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Databases, Genetic ; Evolution, Molecular ; Gene Expression Regulation, Developmental/genetics ; Genome, Human/genetics ; Genomics ; Hominidae/*genetics ; Humans ; Male ; Meiosis/*genetics ; Neanderthals/*genetics ; Selection, Genetic ; Testis ; }, abstract = {About 1-6% of the genetic ancestry of modern humans today originates from admixture with archaic humans. It has recently been shown that autosomal genomic regions with a reduced proportion of Neanderthal and Denisovan ancestries (NA and DA) are significantly enriched in genes that are more expressed in testis than in other tissues. To determine whether a cellular segregation pattern would exist, we combined maps of archaic introgression with a cross-analysis of three transcriptomic datasets deciphering the transcriptional landscape of human gonadal cell types. We reveal that the regions deficient in both NA and DA contain a significant enrichment of genes transcribed in meiotic germ cells. The interbreeding of anatomically modern humans with archaic humans may have introduced archaic-derived alleles that contributed to genetic incompatibilities affecting meiosis that were subsequently purged by natural selection.}, }
@article {pmid28434540, year = {2017}, author = {Ao, H and Liu, CR and Roberts, AP and Zhang, P and Xu, X}, title = {An updated age for the Xujiayao hominin from the Nihewan Basin, North China: Implications for Middle Pleistocene human evolution in East Asia.}, journal = {Journal of human evolution}, volume = {106}, number = {}, pages = {54-65}, doi = {10.1016/j.jhevol.2017.01.014}, pmid = {28434540}, issn = {1095-8606}, mesh = {Animals ; China ; *Electron Spin Resonance Spectroscopy ; *Fossils ; *Hominidae ; Humans ; Molar ; Neanderthals ; Time Factors ; }, abstract = {The Xujiayao site in the Nihewan Basin (North China) is one of the most important Paleolithic sites in East Asia. Twenty Homo fossils, which were previously assigned to an archaic Homo sapiens group, have been excavated along with more than 30,000 lithic artifacts and ∼5000 mammalian fossil specimens. Dating of the Xujiayao hominin has been pursued since its excavation in the 1970s, but its age has remained controversial because of limitations of the dating techniques that have been applied to available materials. Here, we report new ages for the Xujiayao hominin based on combined electron spin resonance (ESR) dating of quartz in the sediments and high-resolution magnetostratigraphy of the fluvio-lacustrine sequence. The magnetostratigraphy suggests that the upper Matuyama and Brunhes polarity chrons are recorded at Xujiayao. The ESR dating results indicate a pooled average age of 260-370 ka for the Homo-bearing layer, which is consistent with its position within the middle Brunhes normal polarity chron indicated by magnetostratigraphy. This age estimate makes the Xujiayao hominin among the oldest mid-Pleistocene hominins with derived Neanderthal traits in East Asia. This age is consistent with the time when early Denisovans, a sister group of Neanderthals, appeared and colonized eastern Eurasia. Our updated age and the Neanderthal-like traits of the Xujiayao Homo fossils, particularly the Denisovan-like molar teeth, make it possible that the Xujiayao hominin could represent an early Denisovan.}, }
@article {pmid28410231, year = {2017}, author = {Heidenreich, B and Denisova, E and Rachakonda, S and Sanmartin, O and Dereani, T and Hosen, I and Nagore, E and Kumar, R}, title = {Genetic alterations in seborrheic keratoses.}, journal = {Oncotarget}, volume = {8}, number = {22}, pages = {36639-36649}, doi = {10.18632/oncotarget.16698}, pmid = {28410231}, issn = {1949-2553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Biomarkers ; DNA Mutational Analysis ; Female ; Gene Expression ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; *Genetic Variation ; Genotype ; Humans ; Keratosis, Seborrheic/*genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Single Nucleotide ; Whole Exome Sequencing ; }, abstract = {Seborrheic keratoses are common benign epidermal lesions that are associated with increased age and sun-exposure. Those lesions despite harboring multiple somatic alterations in contrast to malignant tumors appear to be genetically stable. In order to investigate and characterize the presence of recurrent mutations, we performed exome sequencing on DNA from one seborrheic keratosis lesion and corresponding blood cells from the same patients with follow up investigation of alterations identified by exome sequencing in 24 additional lesions from as many patients. In addition we investigated alterations in all lesions at specific genes loci that included FGFR3, PIK3CA, HRAS, BRAF, CDKN2A and TERT and DHPH3 promoters. The exome sequencing data indicated three mutations per Mb of the targeted sequence. The mutational pattern depicted typical UV signature with majority of alterations being C>T and CC>TT base changes at dipyrimidinic sites. The FGFR3 mutations were the most frequent, detected in 12 of 25 (48%) lesions, followed by the PIK3CA (32%), TERT promoter (24%) and DPH3 promoter mutations (24%). TERT promoter mutations associated with increased age and were present mainly in the lesions excised from head and neck. Three lesions also carried alterations in CDKN2A. FGFR3, TERT and DPH3 expression did not correlate with mutations in the respective genes and promoters; however, increased FGFR3 transcript levels were associated with increased FOXN1 levels, a suggested positive feedback loop that stalls malignant progression. Thus, in this study we report overall mutation rate through exome sequencing and show the most frequent mutations seborrheic keratosis.}, }
@article {pmid28408228, year = {2017}, author = {Kharitonova, MI and Denisova, AO and Andronova, VL and Kayushin, AL and Konstantinova, ID and Kotovskaya, SK and Galegov, GA and Charushin, VN and Miroshnikov, AI}, title = {New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their activity against herpes simplex virus type 1.}, journal = {Bioorganic & medicinal chemistry letters}, volume = {27}, number = {11}, pages = {2484-2487}, doi = {10.1016/j.bmcl.2017.03.100}, pmid = {28408228}, issn = {1464-3405}, mesh = {Acyclovir/pharmacology ; Antiviral Agents/*chemical synthesis/pharmacology ; Benzimidazoles/*chemistry ; Cytosine/analogs & derivatives/pharmacology ; Drug Resistance, Viral/drug effects ; Foscarnet/pharmacology ; Herpesvirus 1, Human/drug effects ; Humans ; Nucleosides/*chemistry/pharmacology ; Organophosphonates/pharmacology ; }, abstract = {Using the enzymatic transglycosylation reaction β-d-ribo- and 2'-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient.}, }
@article {pmid28346564, year = {2017}, author = {Hu, Y and Malyutina, S and Pikhart, H and Peasey, A and Holmes, MV and Hubacek, J and Denisova, D and Nikitin, Y and Bobak, M}, title = {The Relationship between Body Mass Index and 10-Year Trajectories of Physical Functioning in Middle-Aged and Older Russians: Prospective Results of the Russian HAPIEE Study.}, journal = {The journal of nutrition, health & aging}, volume = {21}, number = {4}, pages = {381-388}, doi = {10.1007/s12603-016-0769-z}, pmid = {28346564}, issn = {1760-4788}, support = {081081/Z/06/Z//Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Aging/*physiology ; Body Height ; Body Mass Index ; Body Weight ; Cohort Studies ; Data Collection ; Female ; *Health Status ; Humans ; Male ; Middle Aged ; Obesity/epidemiology/*pathology ; Physical Fitness/*physiology ; Prospective Studies ; Risk Factors ; Russia/epidemiology ; }, abstract = {OBJECTIVE: To investigate the associations of overweight and obesity with longitudinal decline in physical functioning (PF) among middle-aged and older Russians.

DESIGN: Prospective cohort study.

SETTING: Four rounds of data collection in the Russian Health, Alcohol and Psychosocial factors In Eastern Europe study with up to 10 years of follow-up.

PARTICIPANTS: 9,222 men and women aged 45-69 years randomly selected from the population of two districts of Novosibirsk, Russia.

RESULTS: The mean annual decline in the PF score during the follow-up was -1.92 (95% confidence interval -2.17; -1.68) in men and -1.91 (-2.13; -1.68) in women. At baseline, compared with normal weight, obesity classes I and II+ (but not overweight) were associated with significantly lower PF in both sexes. In prospective analyses, the decline in PF was faster in overweight men (difference from normal weight subjects -0.38 [-0.63; -0.14]), class I obese men and women (-0.49 [-0.82; -0.17] and -0.44 [-0.73; -0.15] respectively) and class II+ obese men and women (-1.13 [-1.73; -0.53] and -0.43 [-0.77; -0.09] respectively). Adjustment for physical activity and other covariates did not materially change the results.

METHODS: Participants with and without ASD performed a visuospatial interference task while undergoing functional Magnetic Resonance Imaging (fMRI). We empirically estimated parameters characterizing participants' latencies and their subtle fluctuations (noise accumulation) over the 16-min scan. We modeled hemodynamic activation and used seed-based analyses of neural coupling to study dysfunction in interference-specific connectivity in a subset of ASD participants who were nonparametrically matched to TD participants on age, male-to-female ratio, and magnitude of movement during the scan.

RESULTS: Stochastic patterns of response fluctuations reveal significantly higher noise-to-signal levels and a more random and noisy structure in ASD versus TD participants, and in particular ASD adults who have the greatest clinical autistic deficits. While individuals with ASD show an overall weaker modulation of interference-specific functional connectivity relative to TD individuals, in particular between the seeds of Anterior Cingulate Cortex (ACC) and Inferior Parietal Sulcus (IPS) and the rest of the brain, we found that in ASD, higher uncertainty during the task is linked to increased interference-specific coupling between bilateral anterior insula and prefrontal cortex.

CONCLUSIONS: Subtle and informative differences in the structure of experiencing information exist between ASD and TD individuals. Our findings reveal in ASD an atypical capacity to apply previously perceived information in a manner optimal for adaptive functioning, plausibly revealing suboptimal message-passing across the CNS.}, }
@article {pmid28233034, year = {2017}, author = {Tashi, T and Scott Reading, N and Wuren, T and Zhang, X and Moore, LG and Hu, H and Tang, F and Shestakova, A and Lorenzo, F and Burjanivova, T and Koul, P and Guchhait, P and Wittwer, CT and Julian, CG and Shah, B and Huff, CD and Gordeuk, VR and Prchal, JT and Ge, R}, title = {Gain-of-function EGLN1 prolyl hydroxylase (PHD2 D4E:C127S) in combination with EPAS1 (HIF-2α) polymorphism lowers hemoglobin concentration in Tibetan highlanders.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {95}, number = {6}, pages = {665-670}, doi = {10.1007/s00109-017-1519-3}, pmid = {28233034}, issn = {1432-1440}, mesh = {Acclimatization/*genetics ; Adult ; Altitude ; Asian Continental Ancestry Group/*genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Erythropoietin/blood ; Female ; Ferritins/blood ; Gene-Environment Interaction ; Haplotypes ; Hemoglobins/*analysis ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases/*genetics ; Male ; Polymorphism, Single Nucleotide ; Tibet ; }, abstract = {Tibetans have lived at high altitude for generations and are thought to be genetically adapted to hypoxic environments. Most are protected from hypoxia-induced polycythemia, and a haplotype of EPAS1, encoding hypoxia-inducible factor (HIF-2α), has been associated with lower hemoglobin levels. We earlier reported a Tibetan-specific EGLN1 haplotype encoding PHD2 which abrogates HIF augmentation in hypoxia. We genotyped 347 Tibetan individuals from varying altitudes for both the Tibetan-specific EGLN1 haplotype and 10 candidate SNPs in the EPAS1 haplotype and correlated their association with hemoglobin levels. The effect of the EGLN1 haplotype on hemoglobin exhibited age dependency at low altitude, while at higher altitudes, it showed a trend to lower hemoglobin levels in the presence of the Tibetan-selected EPAS1 rs142764723 C/C allele. The observed gene-environment and gene-gene interactions and the moderate effect of the EGLN1 and EPAS1 haplotypes on hemoglobin indicate that other modifiers exist. It remains to be determined whether a blunting of erythropoiesis or other physiological consequences of HIF downregulation are the primary drivers of these genetic adaptations among Tibetans.

KEY MESSAGE: Most Tibetans are protected from polycythemia while living in high altitude. An EGLN1 co-adapted haplotype, EGLN1 c.12C>G, c.380G>C is uniquely Tibetan. The Tibetan EPAS1 haplotype has introgressed from the Denisovan genome. While EGLN1 and EPAS1 genotypes lower Hb, this study indicates additional Hb modifiers.}, }
@article {pmid28158547, year = {2016}, author = {Povysil, G and Hochreiter, S}, title = {IBD Sharing between Africans, Neandertals, and Denisovans.}, journal = {Genome biology and evolution}, volume = {8}, number = {12}, pages = {3406-3416}, doi = {10.1093/gbe/evw234}, pmid = {28158547}, issn = {1759-6653}, mesh = {Africa ; African Continental Ancestry Group/genetics ; Animals ; Asian Continental Ancestry Group/genetics ; Breeding ; DNA/genetics ; European Continental Ancestry Group/genetics ; *Evolution, Molecular ; *Gene Flow ; Genome ; Hominidae/*genetics ; Humans ; Neanderthals/genetics ; }, abstract = {Interbreeding between ancestors of humans and other hominins outside of Africa has been studied intensively, while their common history within Africa still lacks proper attention. However, shedding light on human evolution in this time period about which little is known, is essential for understanding subsequent events outside of Africa. We investigate the genetic relationships of humans, Neandertals, and Denisovans by identifying very short DNA segments in the 1000 Genomes Phase 3 data that these hominins share identical by descent (IBD). By focusing on low frequency and rare variants, we identify very short IBD segments with high confidence. These segments reveal events from a very distant past because shorter IBD segments are presumably older than longer ones. We extracted two types of very old IBD segments that are not only shared among humans, but also with Neandertals and/or Denisovans. The first type contains longer segments that are found primarily in Asians and Europeans where more segments are found in South Asians than in East Asians for both Neandertal and Denisovan. These longer segments indicate complex admixture events outside of Africa. The second type consists of shorter segments that are shared mainly by Africans and therefore may indicate events involving ancestors of humans and other ancient hominins within Africa. Our results from the autosomes are further supported by an analysis of chromosome X, on which segments that are shared by Africans and match the Neandertal and/or Denisovan genome were even more prominent. Our results indicate that interbreeding with other hominins was a common feature of human evolution starting already long before ancestors of modern humans left Africa.}, }
@article {pmid28146472, year = {2017}, author = {Carus-Cadavieco, M and Gorbati, M and Ye, L and Bender, F and van der Veldt, S and Kosse, C and Börgers, C and Lee, SY and Ramakrishnan, C and Hu, Y and Denisova, N and Ramm, F and Volitaki, E and Burdakov, D and Deisseroth, K and Ponomarenko, A and Korotkova, T}, title = {Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking.}, journal = {Nature}, volume = {542}, number = {7640}, pages = {232-236}, doi = {10.1038/nature21066}, pmid = {28146472}, issn = {1476-4687}, support = {R01 NS067199/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Eating/physiology/psychology ; Energy Metabolism/physiology ; Feeding Behavior/*physiology/psychology ; Gamma Rhythm/*physiology ; Hypothalamus/cytology/*physiology ; Learning ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/physiology ; Reward ; Somatostatin/metabolism ; }, abstract = {Both humans and animals seek primary rewards in the environment, even when such rewards do not correspond to current physiological needs. An example of this is a dissociation between food-seeking behaviour and metabolic needs, a notoriously difficult-to-treat symptom of eating disorders. Feeding relies on distinct cell groups in the hypothalamus, the activity of which also changes in anticipation of feeding onset. The hypothalamus receives strong descending inputs from the lateral septum, which is connected, in turn, with cortical networks, but cognitive regulation of feeding-related behaviours is not yet understood. Cortical cognitive processing involves gamma oscillations, which support memory, attention, cognitive flexibility and sensory responses. These functions contribute crucially to feeding behaviour by unknown neural mechanisms. Here we show that coordinated gamma (30-90 Hz) oscillations in the lateral hypothalamus and upstream brain regions organize food-seeking behaviour in mice. Gamma-rhythmic input to the lateral hypothalamus from somatostatin-positive lateral septum cells evokes food approach without affecting food intake. Inhibitory inputs from the lateral septum enable separate signalling by lateral hypothalamus neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. Upstream, medial prefrontal cortical projections provide gamma-rhythmic inputs to the lateral septum; these inputs are causally associated with improved performance in a food-rewarded learning task. Overall, our work identifies a top-down pathway that uses gamma synchronization to guide the activity of subcortical networks and to regulate feeding behaviour by dynamic reorganization of functional cell groups in the hypothalamus.}, }
@article {pmid28139571, year = {2016}, author = {Khabarova, EA and Denisova, NP and Rogov, DY and Dmitriev, AB}, title = {[The preliminary results of subthalamic nucleus stimulation after destructive surgery in Parkinson's disease].}, journal = {Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko}, volume = {80}, number = {6}, pages = {36-41}, pmid = {28139571}, issn = {0042-8817}, mesh = {Case-Control Studies ; Deep Brain Stimulation/*adverse effects ; Female ; Globus Pallidus/surgery ; Humans ; Male ; Middle Aged ; Motor Activity ; Neurosurgical Procedures/*adverse effects ; Parkinson Disease/surgery/*therapy ; Subthalamic Nucleus/*physiopathology ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate the efficacy of bilateral electrical stimulation (ES) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) after preceding pallidotomy or ventrolateral (VL) thalamotomy.

MATERIAL AND METHODS: The study included 9 patients with bilateral STN ES who had undergone previous unilateral destructive surgery on the subcortical structures: pallidotomy (5 patients) and VL thalamotomy (4). A control group consisted of 9 patients with STN ES, without prior destructive surgery. A clinical and neurological examination included quantitative assessment of motor disturbances using the Hoehn-Yahr scale and Unified Parkinson's disease rating scale (UPDRS). UPDRS was used to evaluate the motor activity (IIIrd part of the scale) and severity of drug-induced dyskinesia and motor fluctuations (IVth part of the scale).

RESULTS: In the group of STN ES with preceding destruction of the subcortical structures, an improvement in motor functions in the early period (6 months) was 45%, and severity of drug-induced complications was decreased by 75%. In a group of STN DBS without destruction, motor disturbances were improved by 61%, and drug-induced complications were decreased by 77%. Improvement in motor functions amounted to 51.9% in patients with preceding pallidotomy (GPi destruction) and 37.5% in a group with preceding VL thalamotomy. The equivalent dose of levodopa was reduced by 51.39%, from 1,008±346 to 490±194, in the study group and by 55.04%, from 963±96 to 433±160, in the control group.

RESULTS: Here, we show that the haplotype block that harbors the deletion (i) retains high allele frequency among extant and ancient human populations; (ii) harbors unusually high nucleotide variation (π, P < 4.1 × 10-3); (iii) contains an excess of intermediate frequency variants (Tajima's D, P < 3.9 × 10-3); and (iv) has an unusually long time to coalescence to the most recent common ancestor (TSel, 0.1 quantile).

METHODS: In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded.

RESULTS: Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile.

SUBJECTS AND METHODS: The Novosibirsk Research Institute of Internal and Preventive Medicine conducted a cross-sectional population-based survey in one of the typical districts of Novosibirsk in 2013-2015. The survey covered 346 men and 408 women. The criteria of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III, 2001), the International Diabetes Federation (IDF, 2005), the Joint Interim Statement (JIS, 2009), and the All-Russian Research Society of Cardiologists (ARRSC, 2009) were used to detect MS. According to the ARRSC criteria, MS was recorded if a waist circumference (WC) was >80 cm for women and >94 cm for men in conjunction with 2 of the following criteria: a blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, high-density lipoprotein (HDL) cholesterol <1.0 mmol/l for men and <1.2 mmol/l for women, low-density lipoprotein (LDL) cholesterol >3.0 mmol/l, and plasma glucose level ≥6.1 mmol/l.

RESULTS: According to the 2009 ARRSC criteria, the prevalence of abdominal obesity, hypertension, hypertriglyceridemia, HDL hypocholestrolemia, LDL hypercholesterolemia, and high plasma glucose level was 42.6, 33.5, 17.5, 24.3, 64.8, and 29%, respectively. The prevalence of MS in 25-45-year-old Novosibirsk people was 17% (19.9% in men and 14.5% in women) according to the 2001 NCEP-ATP III, 27% (29.5% in men and 24.5% in women) according to the 2005 IDF criteria, 30% (35.8% in men and 25% in women) according to the 2009 JIS criteria, and 29.3% (33.2% in men and 26% in women) according to the 2009 ARRSC criteria, this was higher among men than women. There was an increase in the prevalence of MS with age.

METHODS: A total of 24,542 participants aged 45-69 years, randomly selected from populations of Novosibirsk (Russia), Krakow (Poland) and six Czech towns, were included. Depressive symptoms, assessed by the 20-item Center for Epidemiologic Studies Depression (CES-D) scale, were used as both continuous and categorical variables. Data on deaths were obtained from local or national death registers. Associations between depression and mortality were assessed using Cox proportional hazards models.

RESULTS: Over a median of 7 years, 2091 deaths from all causes and 850 CVD deaths occurred in the cohorts. There was a graded association between CES-D score and mortality; the hazard ratio (HR) of CVD mortality for a 1 SD increase in CES-D was 1.20 (95% confidence interval (CI): 1.16-1.24) in men and 1.23 (95% CI: 1.12-1.35) in women; for all-cause mortality, the HRs were 1.13 (95% CI: 1.09-1.18) and 1.17 (95% CI: 1.10-1.25), respectively. The results were similar across countries.

CONCLUSIONS: Depressive symptoms predicted CVD and all-cause mortality independently of a wide range of potential confounders. The association followed a gradient and increased mortality risks were associated with scores below the cut-offs that are commonly used to define 'depression'.}, }
@article {pmid27756828, year = {2017}, author = {Racimo, F and Marnetto, D and Huerta-Sánchez, E}, title = {Signatures of Archaic Adaptive Introgression in Present-Day Human Populations.}, journal = {Molecular biology and evolution}, volume = {34}, number = {2}, pages = {296-317}, doi = {10.1093/molbev/msw216}, pmid = {27756828}, issn = {1537-1719}, support = {R01 HG003229/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptation, Biological/*genetics ; Alleles ; Animals ; Biological Evolution ; Computer Simulation ; DNA, Ancient/*analysis ; Databases, Nucleic Acid ; Evolution, Molecular ; Gene Frequency ; Genetics, Population ; Haplotypes ; Humans ; Neanderthals ; Phylogeny ; Selection, Genetic ; Sequence Analysis, DNA/*methods ; }, abstract = {Comparisons of DNA from archaic and modern humans show that these groups interbred, and in some cases received an evolutionary advantage from doing so. This process-adaptive introgression-may lead to a faster rate of adaptation than is predicted from models with mutation and selection alone. Within the last couple of years, a series of studies have identified regions of the genome that are likely examples of adaptive introgression. In many cases, once a region was ascertained as being introgressed, commonly used statistics based on both haplotype as well as allele frequency information were employed to test for positive selection. Introgression by itself, however, changes both the haplotype structure and the distribution of allele frequencies, thus confounding traditional tests for detecting positive selection. Therefore, patterns generated by introgression alone may lead to false inferences of positive selection. Here we explore models involving both introgression and positive selection to investigate the behavior of various statistics under adaptive introgression. In particular, we find that the number and allelic frequencies of sites that are uniquely shared between archaic humans and specific present-day populations are particularly useful for detecting adaptive introgression. We then examine the 1000 Genomes dataset to characterize the landscape of uniquely shared archaic alleles in human populations. Finally, we identify regions that were likely subject to adaptive introgression and discuss some of the most promising candidate genes located in these regions.}, }
@article {pmid27708712, year = {2016}, author = {Stankiewicz, P}, title = {One pedigree we all may have come from - did Adam and Eve have the chromosome 2 fusion?.}, journal = {Molecular cytogenetics}, volume = {9}, number = {}, pages = {72}, doi = {10.1186/s13039-016-0283-3}, pmid = {27708712}, issn = {1755-8166}, abstract = {BACKGROUND: In contrast to Great Apes, who have 48 chromosomes, modern humans and likely Neandertals and Denisovans have and had, respectively, 46 chromosomes. The reduction in chromosome number was caused by the head-to-head fusion of two ancestral chromosomes to form human chromosome 2 (HSA2) and may have contributed to the reproductive barrier with Great Apes.

RESULTS: Next generation sequencing and molecular clock analyses estimated that this fusion arose prior to our last common ancestor with Neandertal and Denisovan hominins ~ 0.74 - 4.5 million years ago.

HYPOTHESES: I propose that, unlike recurrent Robertsonian translocations in humans, the HSA2 fusion was a single nonrecurrent event that spread through a small polygamous clan population bottleneck. Its heterozygous to homozygous conversion, fixation, and accumulation in the succeeding populations was likely facilitated by an evolutionary advantage through the genomic loss rather than deregulation of expression of the gene(s) flanking the HSA2 fusion site at 2q13.

METHODS: We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.

RESULTS: During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.

RESULTS: 136 patients underwent test stimulation at the Center in 2014. A significant reduction in pain was observed in 75 (55.1%) patients. These patients underwent the second stage of surgery that included implantation of permanent electrodes and a generator. The mean VAS score was 6.5 (maximum: 10; minimum: 5) before surgery, 3.2 at discharge, and 3.1 after 3 and 6 months. The VAS score amounted to 3.6 after 12 months. Complications in the form of pain at the generator implantation site and the need for removal of the system occurred in 2 patients (2.6%), electrode migration was observed in 4 (5.3%) cases.

SUBJECTS AND METHODS: The WHO respiratory symptom questionnaire and the ECRHS screening questionnaire were used for a population-based survey conducted in Novosibirsk to identify respiratory symptoms; 545 people replied to the questions available in the questionnaires. SCL was determined by enzyme immunoassay on a random subsample of 182 examinees.

RESULTS: The incidence of respiratory symptoms was determined among the 25-45-year-old Novosibirsk dwellers: cough (27.7%), more than 3-month cough per year (22%), sputum discharge (25%), forced respiration/wheezing in the past year (22.6%), suffocation fits in the past year (5.3%), and cough/forced respiration/stertor bouts by breathing cold air (14.9%) or contacting animals, plants, or chemical agents (16.5%). There was a significant positive correlation between SCL and the presence of cough, more than 3-month cough per year, sputum discharge, forced respiration/wheezing in the past year (compared to the examinees who did not report these symptoms). The median SCL proved to be significantly higher in the people who complained of cough, more than 3-month cough per year, sputum discharge, and forced respiration/wheezing in the past year (compared to the examinees who did not report these symptoms). The people who had a SCL of more than 3 ng/ml were ascertained to be at higher risk of cough, more than 3-month cough per year, sputum discharge, and forced respiration/wheezing in the past year than those who had a SCL of less than 3 ng/ml.

CONCLUSION: The incidence of respiratory symptoms was determined among the 25-45-year-old Novosibirsk dwellers; SCL was found to be associated with the symptoms characteristic of bronchial obstructive diseases; the expediency of using the SCL threshold of 3 ng/ml as a marker of tobacco smoking was confirmed.}, }
@article {pmid26976447, year = {2016}, author = {Meyer, M and Arsuaga, JL and de Filippo, C and Nagel, S and Aximu-Petri, A and Nickel, B and Martínez, I and Gracia, A and Bermúdez de Castro, JM and Carbonell, E and Viola, B and Kelso, J and Prüfer, K and Pääbo, S}, title = {Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins.}, journal = {Nature}, volume = {531}, number = {7595}, pages = {504-507}, doi = {10.1038/nature17405}, pmid = {26976447}, issn = {1476-4687}, mesh = {Alleles ; Animals ; DNA, Mitochondrial/genetics ; Fossils ; Genome, Mitochondrial/genetics ; Hominidae/classification/*genetics ; Male ; Neanderthals/classification/genetics ; *Phylogeny ; Sequence Alignment ; Spain ; }, abstract = {A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago. An interesting question is how these Middle Pleistocene hominins were related to those who lived in the Late Pleistocene epoch, in particular to Neanderthals in western Eurasia and to Denisovans, a sister group of Neanderthals so far known only from southern Siberia. While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals. However, since the mitochondrial DNA does not reveal the full picture of relationships among populations, we have investigated DNA preservation in several individuals found at Sima de los Huesos. Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.}, }
@article {pmid26966016, year = {2016}, author = {Ghirotto, S and Tassi, F and Barbujani, G and Pattini, L and Hayward, C and Vollenweider, P and Bochud, M and Rampoldi, L and Devuyst, O}, title = {The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human Evolution.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {27}, number = {10}, pages = {2983-2996}, doi = {10.1681/ASN.2015070830}, pmid = {26966016}, issn = {1533-3450}, support = {295733//European Research Council/International ; GGP14263//Telethon/Italy ; MC_PC_U127561128//Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Evolution, Molecular ; Genetic Loci ; Genetic Markers ; Genetic Variation ; Humans ; Urinary Tract Infections/genetics ; Uromodulin/*genetics ; }, abstract = {Common variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD in the general population, increase UMOD expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. To determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead UMOD variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. The T allele of rs4293393, associated with CKD risk, has high frequency in most modern populations and was the one detected in primate genomes. In contrast, we identified only the derived, C allele in Denisovan and Neanderthal genomes. The distribution of the UMOD ancestral allele did not follow the ancestral susceptibility model observed for variants associated with salt-sensitive hypertension. Instead, the global frequencies of the UMOD alleles significantly correlated with pathogen diversity (bacteria, helminths) and prevalence of antibiotic-resistant urinary tract infections (UTIs). The inverse correlation found between urinary levels of uromodulin and markers of UTIs in the general population substantiates the link between UMOD variants and protection against UTIs. These data strongly suggest that the UMOD ancestral allele, driving higher urinary excretion of uromodulin, has been kept at a high frequency because of its protective effect against UTIs.}, }
@article {pmid26911356, year = {2016}, author = {Malyarchuk, BA and Derenko, M and Denisova, G and Woźniak, M and Rogalla, U and Dambueva, I and Grzybowski, T}, title = {Y chromosome haplotype diversity in Mongolic-speaking populations and gene conversion at the duplicated STR DYS385a,b in haplogroup C3-M407.}, journal = {Journal of human genetics}, volume = {61}, number = {6}, pages = {491-496}, doi = {10.1038/jhg.2016.14}, pmid = {26911356}, issn = {1435-232X}, mesh = {Alleles ; Asian Continental Ancestry Group/*genetics ; China ; *Chromosomes, Human, Y ; Cluster Analysis ; Ethnic Groups/genetics ; Evolution, Molecular ; *Gene Conversion ; Gene Frequency ; Genetic Loci ; *Genetic Variation ; *Genetics, Population ; *Haplotypes ; Humans ; Male ; *Microsatellite Repeats ; Mutation ; Russia ; }, abstract = {Y chromosome microsatellite (Y-STR) diversity has been studied in different Mongolic-speaking populations from South Siberia, Mongolia, North-East China and East Europe. The results obtained indicate that the Mongolic-speaking populations clustered into two groups, with one group including populations from eastern part of South Siberia and Central Asia (the Buryats, Barghuts and Khamnigans) and the other group including populations from western part of Central Asia and East Europe (the Mongols and Kalmyks). High frequency of haplogroup C3-M407 (>50%) is present in the Buryats, Barghuts and Khamnigans, whereas in the Mongols and Kalmyks its frequency is much lower. In addition, two allelic combinations in DYS385a,b loci of C3-M407 haplotypes have been observed: the combination 11,18 (as well as 11,17 and 11,19) is frequent in different Mongolic-speaking populations, but the 11,11 branch is present mainly in the Kalmyks and Mongols. Results of locus-specific sequencing suggest that the action of gene conversion is a more likely explanation for origin of homoallelic 11,11 combination. Moreover, analysis of median networks of Y-STR haplotypes demonstrates that at least two gene conversion events can be revealed-one of them has probably occurred among the Mongols, and the other event occurred in the Barghuts. These two events give an average gene conversion rate range of 0.24-7.1 × 10(-3) per generation.}, }
@article {pmid26898827, year = {2016}, author = {Gokhman, D and Meshorer, E and Carmel, L}, title = {Epigenetics: It's Getting Old. Past Meets Future in Paleoepigenetics.}, journal = {Trends in ecology & evolution}, volume = {31}, number = {4}, pages = {290-300}, doi = {10.1016/j.tree.2016.01.010}, pmid = {26898827}, issn = {1872-8383}, mesh = {Animals ; DNA/genetics ; DNA Methylation ; *Epigenesis, Genetic ; Hominidae/*genetics ; }, abstract = {Recent years have witnessed the rise of ancient DNA (aDNA) technology, allowing comparative genomics to be carried out at unprecedented time resolution. While it is relatively straightforward to use aDNA to identify recent genomic changes, it is much less clear how to utilize it to study changes in epigenetic regulation. Here we review recent works demonstrating that highly degraded aDNA still contains sufficient information to allow reconstruction of epigenetic signals, including DNA methylation and nucleosome positioning maps. We discuss challenges arising from the tissue specificity of epigenetics, and show how some of them might in fact turn into advantages. Finally, we introduce a method to infer methylation states in tissues that do not tend to be preserved over time.}, }
@article {pmid26891221, year = {2016}, author = {Balistreri, G and Viiliäinen, J and Turunen, M and Diaz, R and Lyly, L and Pekkonen, P and Rantala, J and Ojala, K and Sarek, G and Teesalu, M and Denisova, O and Peltonen, K and Julkunen, I and Varjosalo, M and Kainov, D and Kallioniemi, O and Laiho, M and Taipale, J and Hautaniemi, S and Ojala, PM}, title = {Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication.}, journal = {PLoS pathogens}, volume = {12}, number = {2}, pages = {e1005424}, doi = {10.1371/journal.ppat.1005424}, pmid = {26891221}, issn = {1553-7374}, mesh = {Cell Cycle Checkpoints/*genetics ; Cell Line, Tumor ; DNA Replication ; Gene Expression Regulation, Viral/*genetics ; Herpesvirus 8, Human/*genetics ; Humans ; RNA, Small Interfering/genetics ; Sarcoma, Kaposi/metabolism/virology ; Stress, Physiological/*genetics ; Virus Activation/physiology ; Virus Latency/genetics ; *Virus Replication/genetics ; }, abstract = {Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.}, }
@article {pmid26886800, year = {2016}, author = {Kuhlwilm, M and Gronau, I and Hubisz, MJ and de Filippo, C and Prado-Martinez, J and Kircher, M and Fu, Q and Burbano, HA and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Rudan, P and Brajkovic, D and Kucan, Ž and Gušic, I and Marques-Bonet, T and Andrés, AM and Viola, B and Pääbo, S and Meyer, M and Siepel, A and Castellano, S}, title = {Ancient gene flow from early modern humans into Eastern Neanderthals.}, journal = {Nature}, volume = {530}, number = {7591}, pages = {429-433}, doi = {10.1038/nature16544}, pmid = {26886800}, issn = {1476-4687}, support = {R01 GM102192/GM/NIGMS NIH HHS/United States ; GM102192/GM/NIGMS NIH HHS/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; }, mesh = {Altitude ; Animals ; Bayes Theorem ; Chromosomes, Human, Pair 21/genetics ; Croatia/ethnology ; Gene Flow/*genetics ; Genome, Human/genetics ; Genomics ; Haplotypes/genetics ; Heterozygote ; Humans ; Hybridization, Genetic/genetics ; Neanderthals/*genetics ; Phylogeny ; Population Density ; Siberia ; Spain/ethnology ; Time Factors ; }, abstract = {It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.}, }
@article {pmid26883865, year = {2016}, author = {Hackinger, S and Kraaijenbrink, T and Xue, Y and Mezzavilla, M and Asan, and van Driem, G and Jobling, MA and de Knijff, P and Tyler-Smith, C and Ayub, Q}, title = {Wide distribution and altitude correlation of an archaic high-altitude-adaptive EPAS1 haplotype in the Himalayas.}, journal = {Human genetics}, volume = {135}, number = {4}, pages = {393-402}, doi = {10.1007/s00439-016-1641-2}, pmid = {26883865}, issn = {1432-1203}, support = {087576//Wellcome Trust/United Kingdom ; 098051//Wellcome Trust/United Kingdom ; }, mesh = {*Altitude ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; *Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; }, abstract = {High-altitude adaptation in Tibetans is influenced by introgression of a 32.7-kb haplotype from the Denisovans, an extinct branch of archaic humans, lying within the endothelial PAS domain protein 1 (EPAS1), and has also been reported in Sherpa. We genotyped 19 variants in this genomic region in 1507 Eurasian individuals, including 1188 from Bhutan and Nepal residing at altitudes between 86 and 4550 m above sea level. Derived alleles for five SNPs characterizing the core Denisovan haplotype (AGGAA) were present at high frequency not only in Tibetans and Sherpa, but also among many populations from the Himalayas, showing a significant correlation with altitude (Spearman's correlation coefficient = 0.75, p value 3.9 × 10(-11)). Seven East- and South-Asian 1000 Genomes Project individuals shared the Denisovan haplotype extending beyond the 32-kb region, enabling us to refine the haplotype structure and identify a candidate regulatory variant (rs370299814) that might be interacting in an additive manner with the derived G allele of rs150877473, the variant previously associated with high-altitude adaptation in Tibetans. Denisovan-derived alleles were also observed at frequencies of 3-14% in the 1000 Genomes Project African samples. The closest African haplotype is, however, separated from the Asian high-altitude haplotype by 22 mutations whereas only three mutations, including rs150877473, separate the Asians from the Denisovan, consistent with distant shared ancestry for African and Asian haplotypes and Denisovan adaptive introgression.}, }
@article {pmid26856178, year = {2015}, author = {Denisov, AP and Semenova, NV and Kun, OA and Denisova, OA}, title = {[COMPREHENSIVE ASSESSMENT OF HEALTH IN BABIES OF EARLY PRESCHOOL AGE].}, journal = {Gigiena i sanitariia}, volume = {94}, number = {8}, pages = {69-72}, pmid = {26856178}, issn = {0016-9900}, mesh = {Adolescent ; Adult ; Child ; *Child Health ; Child, Preschool ; Developmental Disabilities/*epidemiology/etiology ; Female ; *Health Status ; Humans ; Male ; Morbidity/trends ; Siberia/epidemiology ; Socioeconomic Factors ; Young Adult ; }, abstract = {Health of the children's population is one of the most important components of safety of the country. The incidence level in children of early age reflects an interaction of economic, ecological, social and hygienic and medico-organizational factors in society. The issue of the paper is the comprehensive assessment of health of children of the first three years of life upon indices of the morbidity rate, physical development, interrelation of given indices with the structure of the family and their social status. Indices of the physical development of boys in the all age groups exceeded the corresponding indices in girls (p < 0.05). There was also statistically significant and augmentation of indices of body weights of children along with the age (p < 0.05). The highest morbidity rate in children was established in the first year of life, the minimal one--in the third year. In the all age groups diseases of respiratory organs prevailed, at this their proportion in the total amount of diseases in the third year of life considerably exceeded the same in first and second years of life. The highest incidences of children took place in the families formed by juvenile and lonely women. Diseases of digestive organs in the second and third years of life in children from juvenile and lonely mothers were considerably enlarged on frequency (by 1,4-1,7 times), infectious and parasitic diseases (by 1,1-1,7 times) in comparison with children from full families. In the all studied types offamilies and age groups the state of health of children was worse, than in full families. There was substantiated the development of the multilevel system for the prophylaxis of losses of health in children at early preschool age.}, }
@article {pmid26845858, year = {2015}, author = {Malyarchuk, BA and Derenko, MV and Denisova, GA}, title = {[Mitochondrial Genome Variability in the Wolverine (Gulo gulo)].}, journal = {Genetika}, volume = {51}, number = {11}, pages = {1291-1296}, pmid = {26845858}, issn = {0016-6758}, mesh = {Animals ; *Evolution, Molecular ; *Genome, Mitochondrial ; Mustelidae/*genetics ; *Phylogeny ; *Polymorphism, Genetic ; }, abstract = {The nucleotide sequence of an extended mitochondrial genome segment (11473 base pairs in size) was determined in the wolverine (Gulo gulo) from Magadan oblast. Phylogenetic and statistical analyses of mitochondrial DNA (mtDNA) sequences of mustelids showed that the separation of the Gulo phylogenetic branch occurred at the Miocene--early Pliocene (about 5.6 million years ago (MYA)), while the formation of the species G. gulo took place in the Middle Pleistocene (181 and 234 thousand years ago (KYA), according to the results of molecular dating based on the variability of the extended mtDNA segment and the mitochondrial cytochrome b gene, respectively). The molecular data were in agreement with the fossil records for wolverines.}, }
@article {pmid26748514, year = {2016}, author = {Dannemann, M and Andrés, AM and Kelso, J}, title = {Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors.}, journal = {American journal of human genetics}, volume = {98}, number = {1}, pages = {22-33}, doi = {10.1016/j.ajhg.2015.11.015}, pmid = {26748514}, issn = {1537-6605}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Cell Line ; *Haplotypes ; Humans ; Neanderthals/*genetics ; Polymorphism, Single Nucleotide ; Toll-Like Receptors/*genetics ; }, abstract = {Pathogens and the diseases they cause have been among the most important selective forces experienced by humans during their evolutionary history. Although adaptive alleles generally arise by mutation, introgression can also be a valuable source of beneficial alleles. Archaic humans, who lived in Europe and Western Asia for more than 200,000 years, were probably well adapted to this environment and its local pathogens. It is therefore conceivable that modern humans entering Europe and Western Asia who admixed with them obtained a substantial immune advantage from the introgression of archaic alleles. Here we document a cluster of three Toll-like receptors (TLR6-TLR1-TLR10) in modern humans that carries three distinct archaic haplotypes, indicating repeated introgression from archaic humans. Two of these haplotypes are most similar to the Neandertal genome, and the third haplotype is most similar to the Denisovan genome. The Toll-like receptors are key components of innate immunity and provide an important first line of immune defense against bacteria, fungi, and parasites. The unusually high allele frequencies and unexpected levels of population differentiation indicate that there has been local positive selection on multiple haplotypes at this locus. We show that the introgressed alleles have clear functional effects in modern humans; archaic-like alleles underlie differences in the expression of the TLR genes and are associated with increased [corrected] microbial resistance and increased allergic disease in large cohorts. This provides strong evidence for recurrent adaptive introgression at the TLR6-TLR1-TLR10 locus, resulting in differences in disease phenotypes in modern humans.}, }
@article {pmid26719974, year = {2015}, author = {Arciero, E and Biagini, SA and Chen, Y and Xue, Y and Luiselli, D and Tyler-Smith, C and Pagani, L and Ayub, Q}, title = {Genes Regulated by Vitamin D in Bone Cells Are Positively Selected in East Asians.}, journal = {PloS one}, volume = {10}, number = {12}, pages = {e0146072}, doi = {10.1371/journal.pone.0146072}, pmid = {26719974}, issn = {1932-6203}, support = {098051//Wellcome Trust/United Kingdom ; }, mesh = {Asian Continental Ancestry Group/*genetics ; Bone and Bones/*metabolism ; Core Binding Factor Alpha 1 Subunit/genetics ; DNA-Binding Proteins/genetics ; Gene Frequency/genetics ; Haplotypes/genetics ; Humans ; Low Density Lipoprotein Receptor-Related Protein-5/genetics ; Osteoporosis/genetics ; Polymorphism, Single Nucleotide/genetics ; Selection, Genetic/genetics ; Vitamin D/*genetics ; }, abstract = {Vitamin D and folate are activated and degraded by sunlight, respectively, and the physiological processes they control are likely to have been targets of selection as humans expanded from Africa into Eurasia. We investigated signals of positive selection in gene sets involved in the metabolism, regulation and action of these two vitamins in worldwide populations sequenced by Phase I of the 1000 Genomes Project. Comparing allele frequency-spectrum-based summary statistics between these gene sets and matched control genes, we observed a selection signal specific to East Asians for a gene set associated with vitamin D action in bones. The selection signal was mainly driven by three genes CXXC finger protein 1 (CXXC1), low density lipoprotein receptor-related protein 5 (LRP5) and runt-related transcription factor 2 (RUNX2). Examination of population differentiation and haplotypes allowed us to identify several candidate causal regulatory variants in each gene. Four of these candidate variants (one each in CXXC1 and RUNX2 and two in LRP5) had a >70% derived allele frequency in East Asians, but were present at lower (20-60%) frequency in Europeans as well, suggesting that the adaptation might have been part of a common response to climatic and dietary changes as humans expanded out of Africa, with implications for their role in vitamin D-dependent bone mineralization and osteoporosis insurgence. We also observed haplotype sharing between East Asians, Finns and an extinct archaic human (Denisovan) sample at the CXXC1 locus, which is best explained by incomplete lineage sorting.}, }
@article {pmid29889396, year = {2016}, author = {Reshetnikov, OV and Kurilovich, SA and Denisova, DV and Krotov, SA}, title = {PREVALENCE AND RISK FACTORS OF GERD IN ADOLESCENTS IN NOVOSIBIRSK: TEN-YEAR TRENDS.}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {9}, pages = {54-57}, pmid = {29889396}, issn = {1682-8658}, mesh = {Adolescent ; Antibodies, Bacterial/blood ; Female ; Gastroesophageal Reflux/blood/*epidemiology ; Helicobacter Infections/blood/*epidemiology ; *Helicobacter pylori ; Humans ; Immunoglobulin G/blood ; Male ; Prevalence ; Risk Factors ; Siberia/epidemiology ; }, abstract = {The aim of the study was the study of ten-year trends (1999-2009) of GERD symptoms and risk factors in schoolchildren in Novosibirsk from 14 to 17 years.

MATERIALS AND METHODS: The comparison of the results of the screenings performed at 1999 and 2009 was analyzed. Anthropometry, the survey to identify the symptoms of GERD and eating habits, smoking and alcohol consumption, determination of lgG and CagA antibodies to Helicobacterpylori were included at the program of screenings.

RESULTS: No significant dynamics of GER symptoms in adolescents, except weekly heartburn among boys. Among the factors associated with dyspepsia and GER, there have been some mixed changes: the frequency of smoking significantly reduced, but the proportion adolescents with excess body weight have increased. Violations of the regime and diet, and Helicobocrerpylori-infection has not changed significantly.

RESULTS: A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.

CONCLUSIONS: Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.}, }
@article {pmid26673402, year = {2015}, author = {Hammill, JA and VanSeggelen, H and Helsen, CW and Denisova, GF and Evelegh, C and Tantalo, DG and Bassett, JD and Bramson, JL}, title = {Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors.}, journal = {Journal for immunotherapy of cancer}, volume = {3}, number = {}, pages = {55}, doi = {10.1186/s40425-015-0099-4}, pmid = {26673402}, issn = {2051-1426}, abstract = {BACKGROUND: Adoptive cell transfer of tumor-specific T lymphocytes (T cells) is proving to be an effective strategy for treating established tumors in cancer patients. One method of generating these cells is accomplished through engineering bulk T cell populations to express chimeric antigen receptors (CARs), which are specific for tumor antigens. Traditionally, these CARs are targeted against tumor antigens using single-chain antibodies (scFv). Here we describe the use of a designed ankyrin repeat protein (DARPin) as the tumor-antigen targeting domain.

METHODS: We prepared second generation anti-HER2 CARs that were targeted to the tumor antigen by either a DARPin or scFv. The CARs were engineered into human and murine T cells. We then compared the ability of CARs to trigger cytokine production, degranulation and cytotoxicity.

RESULTS: The DARPin CARs displayed reduced surface expression relative to scFv CARs in murine cells but both CARs were expressed equally well on human T cells, suggesting that there may be a processing issue with the murine variants. In both the murine and human systems, the DARPin CARs were found to be highly functional, triggering cytokine and cytotoxic responses that were similar to those triggered by the scFv CARs.

CONCLUSIONS: These findings demonstrate the utility of DARPins as CAR-targeting agents and open up an avenue for the generation of CARs with novel antigen binding attributes.}, }
@article {pmid26664599, year = {2015}, author = {Denisova, YI and Gringolts, ML and Peregudov, AS and Krentsel, LB and Litmanovich, EA and Litmanovich, AD and Finkelshtein, ESh and Kudryavtsev, YV}, title = {Cross-metathesis of polynorbornene with polyoctenamer: a kinetic study.}, journal = {Beilstein journal of organic chemistry}, volume = {11}, number = {}, pages = {1796-1808}, doi = {10.3762/bjoc.11.195}, pmid = {26664599}, issn = {1860-5397}, abstract = {The cross-metathesis of polynorbornene and polyoctenamer in d-chloroform mediated by the 1(st) generation Grubbs' catalyst Cl2(PCy3)2Ru=CHPh is studied by monitoring the kinetics of carbene transformation and evolution of the dyad composition of polymer chains with in situ (1)H and ex situ (13)C NMR spectroscopy. The results are interpreted in terms of a simple kinetic two-stage model. At the first stage of the reaction all Ru-benzylidene carbenes are transformed into Ru-polyoctenamers within an hour, while the polymer molar mass is considerably decreased. The second stage actually including interpolymeric reactions proceeds much slower and takes one day or more to achieve a random copolymer of norbornene and cyclooctene. Its rate is limited by the interaction of polyoctenamer-bound carbenes with polynorbornene units, which is hampered, presumably due to steric reasons. Polynorbornene-bound carbenes are detected in very low concentrations throughout the whole process thus indicating their higher reactivity, as compared with the polyoctenamer-bound ones. Macroscopic homogeneity of the reacting media is proved by dynamic light scattering from solutions containing the polymer mixture and its components. In general, the studied process can be considered as a new way to unsaturated multiblock statistical copolymers. Their structure can be controlled by the amount of catalyst, mixture composition, and reaction time. It is remarkable that this goal can be achieved with a catalyst that is not suitable for ring-opening metathesis copolymerization of norbornene and cis-cyclooctene because of their substantially different monomer reactivities.}, }
@article {pmid26634840, year = {2016}, author = {Denisova, MN and Makarova, EI and Pavlov, IN and Budaeva, VV and Sakovich, GV}, title = {Enzymatic Hydrolysis of Hydrotropic Pulps at Different Substrate Loadings.}, journal = {Applied biochemistry and biotechnology}, volume = {178}, number = {6}, pages = {1196-1206}, doi = {10.1007/s12010-015-1938-y}, pmid = {26634840}, issn = {1559-0291}, mesh = {Cellulase/*chemistry ; Cellulose/chemistry ; Hydrolysis ; Microscopy, Electron, Scanning ; Substrate Specificity ; }, abstract = {Enzymatic hydrolysis of cellulosic raw materials to produce nutrient broths for microbiological synthesis of ethanol and other valuable products is an important field of modern biotechnology. Biotechnological processing implies the selection of an effective pretreatment technique for raw materials. In this study, the hydrotropic treatment increased the reactivity of the obtained substrates toward enzymatic hydrolysis by 7.1 times for Miscanthus and by 7.3 times for oat hulls. The hydrotropic pulp from oat hulls was more reactive toward enzymatic hydrolysis compared to that from Miscanthus, despite that the substrates had similar compositions. As the initial substrate loadings were raised during enzymatic hydrolysis of the hydrotropic Miscanthus and oat hull pulps, the concentration of reducing sugars increased by 34 g/dm(3) and the yield of reducing sugars decreased by 31 %. The findings allow us to predict the efficiency of enzymatic hydrolysis of hydrotropic pulps from Miscanthus and oat hulls when scaling up the process by volume.}, }
@article {pmid26630009, year = {2015}, author = {Sawyer, S and Renaud, G and Viola, B and Hublin, JJ and Gansauge, MT and Shunkov, MV and Derevianko, AP and Prüfer, K and Kelso, J and Pääbo, S}, title = {Nuclear and mitochondrial DNA sequences from two Denisovan individuals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {15696-15700}, doi = {10.1073/pnas.1519905112}, pmid = {26630009}, issn = {1091-6490}, mesh = {Animals ; Base Sequence ; Cell Nucleus/*genetics ; DNA, Mitochondrial/*chemistry ; Evolution, Molecular ; Molecular Sequence Data ; Neanderthals/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans.}, }
@article {pmid26601491, year = {2015}, author = {Malyarchuk, BA and Derenko, MV and Denisova, GA and Litvinov, AN}, title = {[Topological Conflicts in Phylogenetic Analysis of Different Regions of the Sable (Martes zibellina L.) Mitochondrial Genome].}, journal = {Genetika}, volume = {51}, number = {8}, pages = {915-923}, pmid = {26601491}, issn = {0016-6758}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Genome, Mitochondrial/*genetics ; Haplotypes/genetics ; Mustelidae/*genetics ; Mutation ; *Phylogeny ; RNA, Ribosomal/genetics ; }, abstract = {Phylogenetic analysis of different regions of the mitochondrial genome of the sable showed the presence of several topologies of phylogenetic trees, but the most statistically significant topology is A-BC, which was obtained as a result of the analysis of the mitochondrial genome as a whole, as well as of the individual CO1, ND4, and ND5 genes. Analysis of the intergroup divergence of the mtDNA haplotypes (Dxy) indicated that the maximum Dxy values between A and BC groups were accompanied by minimum differences between B and C groups only for six genes showing the A-BC topology (12S rRNA; CO1, CO2, ND4, ND5, and CYTB). It is assumed that the topological conflicts observed in the analysis of individual sable mtDNA genes are associated with the uneven distribution of mutations along the mitochondrial genome and the mitochondrial tree. This may be due to random causes, as well as the nonuniform effect of selection.}, }
@article {pmid26596347, year = {2016}, author = {Racimo, F}, title = {Testing for Ancient Selection Using Cross-population Allele Frequency Differentiation.}, journal = {Genetics}, volume = {202}, number = {2}, pages = {733-750}, doi = {10.1534/genetics.115.178095}, pmid = {26596347}, issn = {1943-2631}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; R01-GM40282/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; *Alleles ; Animals ; Asian Continental Ancestry Group/genetics ; Computer Simulation ; European Continental Ancestry Group/genetics ; Evolution, Molecular ; *Gene Frequency ; *Genetics, Population ; Genome-Wide Association Study ; Genomics/methods ; Humans ; *Models, Genetic ; Neanderthals/genetics ; ROC Curve ; *Selection, Genetic ; }, abstract = {A powerful way to detect selection in a population is by modeling local allele frequency changes in a particular region of the genome under scenarios of selection and neutrality and finding which model is most compatible with the data. A previous method based on a cross-population composite likelihood ratio (XP-CLR) uses an outgroup population to detect departures from neutrality that could be compatible with hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent selection and may miss selective events that happened a long time ago. To overcome this, we developed an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. Our method - called "3-population composite likelihood ratio" (3P-CLR) - outperforms XP-CLR when testing for selection that occurred before two populations split from each other and can distinguish between those events and events that occurred specifically in each of the populations after the split. We applied our new test to population genomic data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of Yoruba and Eurasians, but after their split from Neanderthals, and that could have led to the spread of modern-human-specific phenotypes. We also searched for sweep events that occurred in East Asians, Europeans, and the ancestors of both populations, after their split from Yoruba. In both cases, we are able to confirm a number of regions identified by previous methods and find several new candidates for selection in recent and ancient times. For some of these, we also find suggestive functional mutations that may have driven the selective events.}, }
@article {pmid26567083, year = {2016}, author = {Vyas, DN and Kitchen, A and Miró-Herrans, AT and Pearson, LN and Al-Meeri, A and Mulligan, CJ}, title = {Bayesian analyses of Yemeni mitochondrial genomes suggest multiple migration events with Africa and Western Eurasia.}, journal = {American journal of physical anthropology}, volume = {159}, number = {3}, pages = {382-393}, doi = {10.1002/ajpa.22890}, pmid = {26567083}, issn = {1096-8644}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Africa ; Anthropology, Physical ; Asia, Western ; Bayes Theorem ; Europe ; Genome, Mitochondrial/*genetics ; Haplotypes ; History, Ancient ; *Human Migration ; Humans ; Phylogeny ; Yemen ; }, abstract = {OBJECTIVES: Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the first successful global dispersal. This initial migration may have passed through Yemen, a region that has experienced multiple migrations events with Africa and Eurasia throughout human history. We use Bayesian phylogenetics to determine how ancient and recent migrations have shaped Yemeni mitogenomic variation.

MATERIALS AND METHODS: We sequenced 113 mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as these groups have the oldest evolutionary history outside of Africa. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenomes in order to determine the age of Yemeni-specific clades.

RESULTS: As defined by Yemeni monophyly, Yemeni in situ evolution is limited to the Holocene or latest Pleistocene (ages of clades in subhaplogroups L3b1a1a, L3h2, L3x1, M1a1f, M1a5, N1a1a3, and N1a3 range from 2 to 14 kya) and is often situated within broader Horn of Africa/southern Arabia in situ evolution (L3h2, L3x1, M1a1f, M1a5, and N1a1a3 ages range from 7 to 29 kya). Five subhaplogroups show no monophyly and are candidates for Holocene migration into Yemen (L0a2a2a, L3d1a1a, L3i2, M1a1b, and N1b1a).

PURPOSE: To estimate the information content of alginate test in the diagnosis of GERD in the age aspect.

MATERIALS AND METHODS: Core group--those aged 60-86 years, the comparative group 25-59 years. Two subgroups: the results of alginate test with a positive result and a negative result. Calculated the body mass index, endoscopic examination was performed daily pH--metry.

RESULTS: There is direct correlation between the test result and clinical and instrumental signs of GERD. Alginate test can be used as a screening method for the early diagnosis in patients with GERD different age groups.}, }
@article {pmid26325393, year = {2016}, author = {Denisova, K and Feldman, J and Su, X and Singh, M}, title = {Investigating shape representation using sensitivity to part- and axis-based transformations.}, journal = {Vision research}, volume = {126}, number = {}, pages = {347-361}, doi = {10.1016/j.visres.2015.07.004}, pmid = {26325393}, issn = {1878-5646}, support = {R01 EY021494/EY/NEI NIH HHS/United States ; }, mesh = {*Discrimination (Psychology) ; *Form Perception ; Humans ; Judgment ; Photic Stimulation/methods ; Psychometrics ; Rotation ; Sensory Thresholds ; *Visual Perception ; }, abstract = {Part- and axis-based approaches organize shape representations in terms of simple parts and their spatial relationships. Shape transformations that alter qualitative part structure have been shown to be more detectable than those that preserve it. We compared sensitivity to various transformations that change quantitative properties of parts and their spatial relationships, while preserving qualitative part structure. Shape transformations involving changes in length, width, curvature, orientation and location were applied to a small part attached to a larger base of a two-part shape. Increment thresholds were estimated for each transformation using a 2IFC procedure. Thresholds were converted into common units of shape difference to enable comparisons across transformations. Higher sensitivity was consistently found for transformations involving a parameter of a single part (length, width, curvature) than those involving spatial relations between two parts (relative orientation and location), suggesting a single-part superiority effect. Moreover, sensitivity to shifts in part location - a biomechanically implausible shape transformation - was consistently poorest. The influence of region-based geometry was investigated via stereoscopic manipulation of figure and ground. Sensitivity was compared across positive parts (protrusions) and negative parts (indentations) for transformations involving a change in orientation or location. For changes in part orientation (biomechanically plausible), sensitivity was better for positive than negative parts; whereas for changes in part location (biomechanically implausible), no systematic difference was observed.}, }
@article {pmid26281203, year = {2015}, author = {Rekhtina, IG and Zakharova, EV and Stolyarevich, ES and Sinitsina, MN and Denisova, EN}, title = {[The concurrence of light-chain deposition disease, AL-amyloidosis, and cast nephropathy in a patient with multiple myeloma].}, journal = {Terapevticheskii arkhiv}, volume = {87}, number = {6}, pages = {98-101}, pmid = {26281203}, issn = {0040-3660}, mesh = {Amyloidosis/*complications/diagnosis ; Fatal Outcome ; Humans ; Immunoglobulin Light Chains/*metabolism ; Immunoglobulin Light-chain Amyloidosis ; Kidney Diseases/*complications/diagnosis ; Male ; Middle Aged ; Multiple Myeloma/*complications/diagnosis ; Paraproteinemias/*complications/diagnosis/metabolism ; }, abstract = {Despite of the fact that their clinical manifestations are similar, AL-amyloidosis (AL-A) and light chain deposition disease (LCDD) are individual nosological entities in view of considerable differences in their pathogenesis and pathomorphology. The paper describes a rare case of the concurrence of LCDD and AL-A in a patient with multiple myeloma. Clinically, there was dialysis-dependent renal failure, flail leg syndrome, myocardiopathy, and rhabdomyolysis. At the disease onset, his nephrobiopsy specimen could diagnose LCDD and myeloma or cast nephropathy. The disease was characterized by an aggressive course. Despite the administration of innovative agents, the patient had a short-term remission and died from disease progression. Autopsy additionally revealed amyloid deposition in the heart and kidney. The development of AL-A in the presence of prior LCDD may reflect the progression of the tumor and the appearance of an additional subclone of plasma cells that produce amyloidogenic light chains. The uncommonness of this case is that renal amyloid was found in the tubular casts and absent in the glomeruli, which may be considered as a special form--tubular AL-amyloidosis.}, }
@article {pmid26249230, year = {2015}, author = {Sudmant, PH and Mallick, S and Nelson, BJ and Hormozdiari, F and Krumm, N and Huddleston, J and Coe, BP and Baker, C and Nordenfelt, S and Bamshad, M and Jorde, LB and Posukh, OL and Sahakyan, H and Watkins, WS and Yepiskoposyan, L and Abdullah, MS and Bravi, CM and Capelli, C and Hervig, T and Wee, JT and Tyler-Smith, C and van Driem, G and Romero, IG and Jha, AR and Karachanak-Yankova, S and Toncheva, D and Comas, D and Henn, B and Kivisild, T and Ruiz-Linares, A and Sajantila, A and Metspalu, E and Parik, J and Villems, R and Starikovskaya, EB and Ayodo, G and Beall, CM and Di Rienzo, A and Hammer, MF and Khusainova, R and Khusnutdinova, E and Klitz, W and Winkler, C and Labuda, D and Metspalu, M and Tishkoff, SA and Dryomov, S and Sukernik, R and Patterson, N and Reich, D and Eichler, EE}, title = {Global diversity, population stratification, and selection of human copy-number variation.}, journal = {Science (New York, N.Y.)}, volume = {349}, number = {6253}, pages = {aab3761}, doi = {10.1126/science.aab3761}, pmid = {26249230}, issn = {1095-9203}, support = {5DP1ES022577 05/DP/NCCDPHP CDC HHS/United States ; HHSN26120080001E//PHS HHS/International ; 1R01DK104339-01/DK/NIDDK NIH HHS/United States ; 261213//European Research Council/International ; R01 DK104339/DK/NIDDK NIH HHS/United States ; R01 HL119577/HL/NHLBI NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; 1R01GM113657-01/GM/NIGMS NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; 098051//Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; R01 GM113657/GM/NIGMS NIH HHS/United States ; T32 GM007266/GM/NIGMS NIH HHS/United States ; 2R01HG002385/HG/NHGRI NIH HHS/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; DP1 ES022577/ES/NIEHS NIH HHS/United States ; }, mesh = {African Continental Ancestry Group/classification/genetics ; Animals ; *DNA Copy Number Variations ; *Evolution, Molecular ; *Gene Duplication ; Genome, Human/*genetics ; Hominidae/genetics ; Humans ; Oceanic Ancestry Group/classification/genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Population/*genetics ; Selection, Genetic ; *Sequence Deletion ; }, abstract = {In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide-variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.}, }
@article {pmid26206078, year = {2015}, author = {Kutzner, A and Pramanik, S and Kim, PS and Heese, K}, title = {All-or-(N)One - an epistemological characterization of the human tumorigenic neuronal paralogous FAM72 gene loci.}, journal = {Genomics}, volume = {106}, number = {5}, pages = {278-285}, doi = {10.1016/j.ygeno.2015.07.003}, pmid = {26206078}, issn = {1089-8646}, mesh = {Animals ; Carrier Proteins/*genetics ; Chromosomes, Human, Pair 1 ; Computer Simulation ; Genes ; Genetic Loci ; Genomics ; Hominidae/genetics ; Humans ; Neanderthals/genetics ; Neoplasm Proteins/*genetics ; Phylogeny ; Proteins ; Segmental Duplications, Genomic ; }, abstract = {FAM72 is a novel neuronal progenitor cell (NPC) self-renewal supporting protein expressed under physiological conditions at low levels in other tissues. Accumulating data indicate the potential pivotal tumourigenic effects of FAM72. Our in silico human genome-wide analysis (GWA) revealed that the FAM72 gene family consists of four human-specific paralogous members, all of which are located on chromosome (chr) 1. Unique asymmetric FAM72 segmental gene duplications are most likely to have occurred in conjunction with the paired genomic neighbour SRGAP2 (SLIT-ROBO Rho GTPase activating protein), as both genes have four paralogues in humans but only one vertebra-emerging orthologue in all other species. No species with two or three FAM72/SRGAP2 gene pairs could be identified, and the four exclusively human-defining ohnologues, with different mutation patterns in Homo neanderthalensis and Denisova hominin, may remain under epigenetic control through long non-coding (lnc) RNAs.}, }
@article {pmid26176239, year = {2015}, author = {Blank, M and Blank, O and Myasnikova, E and Denisova, D}, title = {Peculiarities of Anxiety Score Distribution in Adult Cancer Patients.}, journal = {Journal of psychosocial oncology}, volume = {33}, number = {5}, pages = {551-560}, doi = {10.1080/07347332.2015.1067280}, pmid = {26176239}, issn = {1540-7586}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Anxiety/*psychology ; Case-Control Studies ; Female ; Humans ; Male ; Neoplasms/drug therapy/*psychology ; Pregnancy ; Psychiatric Status Rating Scales ; Remission Induction ; }, abstract = {The goal of the present research is to investigate and analyze possible peculiarities of the psychological state of cancer patients undergoing treatment. Scores characterizing the trait and state anxiety were acquired using the Integrative Anxiety Test from four groups: adults with no appreciable disease, pregnant women, cancer patients examined during the specific antitumor treatment, and cancer patients brought into lasting clinical remission. Statistical analysis of the testing results revealed the bimodal type of the distribution of scores. The only statistically significant exception was the distribution of the state anxiety scores in cancer patients undergoing treatment that was clearly unimodal.}, }
@article {pmid26156123, year = {2015}, author = {Fish, I and Boissinot, S}, title = {Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates.}, journal = {Immunogenetics}, volume = {67}, number = {9}, pages = {487-499}, doi = {10.1007/s00251-015-0855-0}, pmid = {26156123}, issn = {1432-1211}, support = {P51 OD011133/OD/NIH HHS/United States ; P51 RR013986/RR/NCRR NIH HHS/United States ; }, mesh = {2',5'-Oligoadenylate Synthetase/*genetics ; Amino Acid Sequence ; Animals ; Base Sequence ; Disease Resistance/*genetics ; Evolution, Molecular ; Haplotypes/*genetics ; Macaca fascicularis/genetics/immunology ; Macaca mulatta/genetics/immunology ; Papio anubis/genetics/immunology ; Papio papio/genetics/immunology ; Polymorphism, Genetic/*genetics ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under long-term balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNA-binding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism.}, }
@article {pmid26122933, year = {2015}, author = {VanSeggelen, H and Hammill, JA and Dvorkin-Gheva, A and Tantalo, DG and Kwiecien, JM and Denisova, GF and Rabinovich, B and Wan, Y and Bramson, JL}, title = {T Cells Engineered With Chimeric Antigen Receptors Targeting NKG2D Ligands Display Lethal Toxicity in Mice.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {23}, number = {10}, pages = {1600-1610}, doi = {10.1038/mt.2015.119}, pmid = {26122933}, issn = {1525-0024}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adoptive Transfer ; Animals ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cyclophosphamide/pharmacology ; Cytokines/metabolism ; *Cytotoxicity, Immunologic ; Disease Models, Animal ; Female ; Gene Expression ; Genetic Vectors/genetics ; Immunotherapy, Adoptive ; Ligands ; Mice ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Neoplasms/genetics/immunology/pathology/therapy ; Pneumonia/immunology/metabolism/pathology ; Receptors, Antigen, T-Cell/genetics/metabolism ; Receptors, Immunologic/genetics/metabolism ; *Recombinant Fusion Proteins ; Retroviridae/genetics ; T-Lymphocytes/immunology/metabolism ; Transplantation Conditioning ; }, abstract = {Ligands for the NKG2D receptor are overexpressed on tumors, making them interesting immunotherapy targets. To assess the tumoricidal properties of T cells directed to attack NKG2D ligands, we engineered murine T cells with two distinct NKG2D-based chimeric antigen receptors (CARs): (i) a fusion between the NKG2D receptor and the CD3ζ chain and (ii) a conventional second-generation CAR, where the extracellular domain of NKG2D was fused to CD28 and CD3ζ. To enhance the CAR surface expression, we also engineered T cells to coexpress DAP10. In vitro functionality and surface expression levels of all three CARs was greater in BALB/c T cells than C57BL/6 T cells, indicating strain-specific differences. Upon adoptive transfer of NKG2D-CAR-T cells into syngeneic animals, we observed significant clinical toxicity resulting in morbidity and mortality. The severity of these toxicities varied between the CAR configurations and paralleled their in vitro NKG2D surface expression. BALB/c mice were more sensitive to these toxicities than C57BL/6 mice, consistent with the higher in vitro functionality of BALB/c T cells. Treatment with cyclophosphamide prior to adoptive transfer exacerbated the toxicity. We conclude that while NKG2D ligands may be useful targets for immunotherapy, the pursuit of NKG2D-based CAR-T cell therapies should be undertaken with caution.}, }
@article {pmid26104010, year = {2015}, author = {Qin, P and Stoneking, M}, title = {Denisovan Ancestry in East Eurasian and Native American Populations.}, journal = {Molecular biology and evolution}, volume = {32}, number = {10}, pages = {2665-2674}, doi = {10.1093/molbev/msv141}, pmid = {26104010}, issn = {1537-1719}, mesh = {Animals ; Consanguinity ; Gene Flow ; *Genealogy and Heraldry ; Geography ; Hominidae/genetics ; Humans ; Indians, North American/*genetics ; Models, Genetic ; Oceanic Ancestry Group/genetics ; Siberia ; }, abstract = {Although initial studies suggested that Denisovan ancestry was found only in modern human populations from island Southeast Asia and Oceania, more recent studies have suggested that Denisovan ancestry may be more widespread. However, the geographic extent of Denisovan ancestry has not been determined, and moreover the relationship between the Denisovan ancestry in Oceania and that elsewhere has not been studied. Here we analyze genome-wide single nucleotide polymorphism data from 2,493 individuals from 221 worldwide populations, and show that there is a widespread signal of a very low level of Denisovan ancestry across Eastern Eurasian and Native American (EE/NA) populations. We also verify a higher level of Denisovan ancestry in Oceania than that in EE/NA; the Denisovan ancestry in Oceania is correlated with the amount of New Guinea ancestry, but not the amount of Australian ancestry, indicating that recent gene flow from New Guinea likely accounts for signals of Denisovan ancestry across Oceania. However, Denisovan ancestry in EE/NA populations is equally correlated with their New Guinea or their Australian ancestry, suggesting a common source for the Denisovan ancestry in EE/NA and Oceanian populations. Our results suggest that Denisovan ancestry in EE/NA is derived either from common ancestry with, or gene flow from, the common ancestor of New Guineans and Australians, indicating a more complex history involving East Eurasians and Oceanians than previously suspected.}, }
@article {pmid26081318, year = {2015}, author = {Katamanova, EV and Rukavishnikov, VS and Lakhman, OL and Shevchenko, OI and Denisova, IA}, title = {[Cognitive impairment in a toxic lesion of the brain].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {115}, number = {2}, pages = {11-15}, pmid = {26081318}, issn = {1997-7298}, mesh = {Alcoholism/*complications/physiopathology ; Brain/*pathology ; Brain Diseases/*complications/diagnosis/physiopathology ; Cognition/*physiology ; Cognition Disorders/diagnosis/*etiology/physiopathology ; Electroencephalography ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Memory/*physiology ; Mercury Poisoning, Nervous System/*complications/physiopathology ; Middle Aged ; Neuropsychological Tests ; Severity of Illness Index ; Time Factors ; }, abstract = {OBJECTIVE: To identify features of cognitive impairment in patients with toxic (mercury or alcohol) encephalopathy.

MATERIAL AND METHODS: The study involved 36 patients with chronic mercury intoxication and 30 people with chronic alcoholism. A control group included 30 age-matched healthy men who were not exposed to toxic substances and alcohol abuse. All patients underwent neuropsychological examination, which involved a set of neuropsychological Luria rated memory status, praxis, gnosis and speeches. MMSE and FAB were used for the diagnosis of moderate cognitive impairment. Computer electroencephalography and cognitive evoked potentials method were used as well.

MATERIAL AND METHODS: A total of 54 patients (96 eyes) aged 18-30 with high myopia and signs of optic neuropathy were observed. The main group consisted of 20 patients (28 eyes) who underwent meridional scleral reinforcement with type I collagen-based implant placed over the posterior segment. The control group included 34 patients (68 eyes) who were given a 10-day vitamin and vascular therapy course. In most of the controls (21 patient, 21 eyes) indirect revascularization with ligation of the superficial temporal artery was performed. Ophthalmological examination was done before the beginning of the treatment and then at 1, 6, and 12 months. Results. At the end of the follow-up period best corrected visual acuity in the main group was 19.2% higher, on average, than baseline values, but remained unchanged in the controls. Light sensitivity of the retina in both group increased by 7% and 2% respectively. Electrically evoked phosphene thresholds decreased by 22.5% and 10.4% respectively. The main group also demonstrated a near-constant mean peripapillary nerve fiber layer (RNFL) thickness and a 16.4% higher than baseline blood flow velocity in the ophthalmic artery. In the control group the latter parameter showed no change.

CONCLUSIONS: Scleral reinforcement surgery in patients with high myopia complicated by optic neuropathy enables improvement of visual functions and regional blood flow as well as stabilization of RNFL thickness and volume, thus, preventing subsequent development of optic nerve atrophy.}, }
@article {pmid26073780, year = {2015}, author = {Lou, H and Lu, Y and Lu, D and Fu, R and Wang, X and Feng, Q and Wu, S and Yang, Y and Li, S and Kang, L and Guan, Y and Hoh, BP and Chung, YJ and Jin, L and Su, B and Xu, S}, title = {A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence.}, journal = {American journal of human genetics}, volume = {97}, number = {1}, pages = {54-66}, doi = {10.1016/j.ajhg.2015.05.005}, pmid = {26073780}, issn = {1537-6605}, mesh = {Adaptation, Biological/*genetics ; Algorithms ; *Altitude ; Animals ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; DNA Copy Number Variations/*genetics ; Ethnic Groups/*genetics ; *Evolution, Molecular ; Genetics, Population ; Hemoglobins/genetics/metabolism ; Hominidae/*genetics ; Humans ; Linkage Disequilibrium ; Microarray Analysis/methods ; Molecular Sequence Data ; Polymerase Chain Reaction/methods ; Sequence Analysis, DNA ; Tibet ; }, abstract = {Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10(-15)). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276-46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r(2) = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1.}, }
@article {pmid26072518, year = {2015}, author = {Hoover, KC and Gokcumen, O and Qureshy, Z and Bruguera, E and Savangsuksa, A and Cobb, M and Matsunami, H}, title = {Global Survey of Variation in a Human Olfactory Receptor Gene Reveals Signatures of Non-Neutral Evolution.}, journal = {Chemical senses}, volume = {40}, number = {7}, pages = {481-488}, doi = {10.1093/chemse/bjv030}, pmid = {26072518}, issn = {1464-3553}, support = {DC005782/DC/NIDCD NIH HHS/United States ; }, mesh = {Alleles ; Base Sequence ; DNA/genetics ; *Evolution, Molecular ; Genetic Variation/*genetics ; Humans ; Polymorphism, Single Nucleotide/genetics ; Receptors, Odorant/*genetics ; }, abstract = {Allelic variation at 4 loci in the human olfactory receptor gene OR7D4 is associated with perceptual variation in the sex steroid-derived odorants, androstenone, and androstadienone. Androstadienone has been linked with chemosensory identification whereas androstenone makes pork from uncastrated pigs distasteful ("boar taint"). In a sample of 2224 individuals from 43 populations, we identified 45 OR7D4 single nucleotide polymorphisms. Coalescent modeling of frequency-site-spectrum-based statistics identified significant deviation from neutrality in human OR7D4; individual populations with statistically significant deviations from neutrality include Gujarati, Beijing Han, Great Britain, Iberia, and Puerto Rico. Analysis of molecular variation values indicated statistically significant population differentiation driven mainly by the 4 alleles associated with androstenone perception variation; however, fixation values were low suggesting that genetic structure may not have played a strong role in creating these group divisions. We also studied OR7D4 in the genomes of extinct members of the human lineage: Altai Neandertal and Denisovan. No variants were identified in Altai but 2 were in Denisova, one of which is shared by modern humans and one of which is novel. A functional test of modern human and a synthesized mutant Denisova OR7D4 indicated no statistically significant difference in responses to androstenone between the 2 species. Our results suggest non-neutral evolution for an olfactory receptor gene.}, }
@article {pmid26017008, year = {2015}, author = {Fontes, JD and Ramsey, J and Polk, JM and Koop, A and Denisova, JV and Belousov, AB}, title = {Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0125395}, doi = {10.1371/journal.pone.0125395}, pmid = {26017008}, issn = {1932-6203}, support = {P20 GM104936/GM/NIGMS NIH HHS/United States ; R21 NS076925/NS/NINDS NIH HHS/United States ; P30 AG035982/AG/NIA NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; UL1 TR000001/TR/NCATS NIH HHS/United States ; R21NS076925/NS/NINDS NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Cell Death/genetics/physiology ; Cell Survival/genetics/physiology ; Cells, Cultured ; Connexins/genetics/metabolism ; Gap Junctions/*metabolism ; Genetic Vectors/genetics ; HeLa Cells ; Humans ; Lentivirus/genetics ; Mice ; Mice, Knockout ; Receptors, N-Methyl-D-Aspartate/genetics/metabolism ; }, abstract = {Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed.}, }
@article {pmid26000734, year = {2015}, author = {Kari, L and Hill, KA and Sayem, AS and Karamichalis, R and Bryans, N and Davis, K and Dattani, NS}, title = {Mapping the space of genomic signatures.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0119815}, doi = {10.1371/journal.pone.0119815}, pmid = {26000734}, issn = {1932-6203}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; *Models, Theoretical ; }, abstract = {We propose a computational method to measure and visualize interrelationships among any number of DNA sequences allowing, for example, the examination of hundreds or thousands of complete mitochondrial genomes. An "image distance" is computed for each pair of graphical representations of DNA sequences, and the distances are visualized as a Molecular Distance Map: Each point on the map represents a DNA sequence, and the spatial proximity between any two points reflects the degree of structural similarity between the corresponding sequences. The graphical representation of DNA sequences utilized, Chaos Game Representation (CGR), is genome- and species-specific and can thus act as a genomic signature. Consequently, Molecular Distance Maps could inform species identification, taxonomic classifications and, to a certain extent, evolutionary history. The image distance employed, Structural Dissimilarity Index (DSSIM), implicitly compares the occurrences of oligomers of length up to k (herein k = 9) in DNA sequences. We computed DSSIM distances for more than 5 million pairs of complete mitochondrial genomes, and used Multi-Dimensional Scaling (MDS) to obtain Molecular Distance Maps that visually display the sequence relatedness in various subsets, at different taxonomic levels. This general-purpose method does not require DNA sequence alignment and can thus be used to compare similar or vastly different DNA sequences, genomic or computer-generated, of the same or different lengths. We illustrate potential uses of this approach by applying it to several taxonomic subsets: phylum Vertebrata, (super)kingdom Protista, classes Amphibia-Insecta-Mammalia, class Amphibia, and order Primates. This analysis of an extensive dataset confirms that the oligomer composition of full mtDNA sequences can be a source of taxonomic information. This method also correctly finds the mtDNA sequences most closely related to that of the anatomically modern human (the Neanderthal, the Denisovan, and the chimp), and that the sequence most different from it in this dataset belongs to a cucumber.}, }
@article {pmid25956332, year = {2015}, author = {Solovyeva, EV and Myund, LA and Denisova, AS}, title = {Surface enhanced Raman scattering of new acridine based fluorophore adsorbed on silver electrode.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {149}, number = {}, pages = {196-200}, doi = {10.1016/j.saa.2015.04.092}, pmid = {25956332}, issn = {1873-3557}, abstract = {4,5-Bis(N,N-di(2-hydroxyethyl)iminomethyl)acridine (BHIA) is a new acridine based fluoroionophore and a highly-selective sensor for cadmium ion. The direct interaction of the aromatic nitrogen atom with a surface is impossible since there are bulky substituents in the 4,5-positions of the acridine fragment. Nevertheless BHIA molecule shows a reliable SERS spectrum while adsorbed on a silver electrode. The analysis of SERS spectra pH dependence reveals that BHIA species adsorbed on a surface can exist in both non-protonated and protonated forms. The adsorption of BHIA from alkaline solution is accompanied by carbonaceous species formation at the surface. The intensity of such "carbon bands" turned out to be related with the supporting electrolyte (KCl) concentration. Upon lowering the electrode potential the SERS spectra of BHIA do not undergo changes but the intensity of bands decreases. This indicates that the adsorption mechanism on the silver surface is realized via aromatic system of acridine fragment. In case of such an adsorption mechanism the chelate fragment of the BHIA molecule is capable of interaction with the solution components. Addition of Cd(2+) ions to a system containing BHIA adsorbed on a silver electrode in equilibrium with the solution leads to the formation of BHIA/Cd(2+) complex which desorption causes the loss of SERS signal.}, }
@article {pmid25857197, year = {2015}, author = {Maliarchuk, BA and Derenko, MV and Denisova, GA}, title = {[Phylogenetic relationships among Asiatic salamanders of the genus Salamandrella based on variability of nuclear genes].}, journal = {Genetika}, volume = {51}, number = {1}, pages = {101-108}, pmid = {25857197}, issn = {0016-6758}, mesh = {Amphibian Proteins/*genetics ; Animals ; Cell Nucleus/genetics ; *Phylogeny ; Salamandridae/*genetics ; Siberia ; Species Specificity ; }, abstract = {Based on sequence variation of three nuclear genome genes (BDNF, POMC, and RAG1), the phylogenetic relationships among Asiatic salamanders of the genus Salamandrella, Siberian salamander (S. keyserlingii) and Schrenk salamander (S. schrenkii), were examined. Both species demonstrated high levels of heterozygosity determined by intraspecific polymorphism. Fixed interspecific differences were revealed at one nucleotide position of the RAG1 gene, and thus the level of interspecific divergence over the three genes constituted only 0.04%. Analysis of the RAG1 polymorphism across the whole range of S. keyserlingii showed that only one gene variant, encoding for modified RAG1 recombinase, had the highest distribution to the north of the Amur region (west and northeast of Siberia). It is possible that the changes in the RAG1 gene in Siberian salamander are of an adaptive nature. However, cases of interspecific hybridization were identified in Jewish autonomous oblast (JAO), which contains one of the range borders between the two Salamandrella species.}, }
@article {pmid25831703, year = {2014}, author = {Musaeva, TS and Berdnikov, AP and Goncharenko, SI and Denisova, EA}, title = {[Efficiency of high-volume hemofiltration in patients with severe sepsis and intracranial hypertension].}, journal = {Anesteziologiia i reanimatologiia}, volume = {59}, number = {6}, pages = {48-51}, pmid = {25831703}, issn = {0201-7563}, mesh = {APACHE ; Carbon Dioxide/blood ; Hemodynamics/physiology ; Hemofiltration/adverse effects/*methods ; Humans ; Intracranial Hypertension/blood/etiology/physiopathology/*therapy ; Intracranial Pressure/physiology ; Oxygen/blood ; Retrospective Studies ; Sepsis/blood/complications/physiopathology/*therapy ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {We performed a retrospective study in 68 patients (144 procedures) with severe sepsis and intracranial hypertension measured by the pressure in the central retinal vein. The patients underwent high-volume hemofiltration (HV-HF) for extrarenal indications. Increased pressure in the central retinal vein was accompanied by critical points of cerebral perfusion pressure and the growth of neurological deficit with inhibition level of consciousness to coma 1. In this case, IHV-HF may be associated with the formation of the critical points of cerebral perfihsion and severe disorders of microcirculation and the lack of resolution of tissue hypoperfusion. In case of intracranial hypertension IHV-HF is not effective in the category of patients where there is a combination ΔpCO2 > 5.9 mm Hg level and GCS <10 points.}, }
@article {pmid25816525, year = {2014}, author = {Karal'nik, BV and Ponomareva, TS and Deriabin, PN and Denisova, TG and Mel'nikova, NN and Tugambaev, TI and Atshabar, BB and Zakarian, SB}, title = {[Effect of immune modulation on immunogenic and protective activity of a live plague vaccine].}, journal = {Zhurnal mikrobiologii, epidemiologii, i immunobiologii}, volume = {}, number = {6}, pages = {108-112}, pmid = {25816525}, issn = {0372-9311}, mesh = {Animals ; Antibodies, Bacterial/*biosynthesis ; Antigens, Bacterial/immunology ; Gene Expression ; Guinea Pigs ; Immunity, Cellular/drug effects ; Immunization ; Immunoglobulin G/*biosynthesis ; Immunologic Factors/*administration & dosage/immunology ; Injections, Intravenous ; Interleukin-1beta/*administration & dosage/immunology ; Piperazines/*administration & dosage/immunology ; Plague/blood/immunology/microbiology/*prevention & control ; Plague Vaccine/*administration & dosage/immunology ; Polymers/*administration & dosage ; Rabbits ; Receptors, Antigen, T-Cell/genetics/immunology ; Vaccines, Attenuated ; Yersinia pestis/immunology ; }, abstract = {AIM: Comparative evaluation of the effect of polyoxidonium and betaleukin on immunogenic and protective activity of a live plague vaccine in model animal experiments.

MATERIALS AND METHODS: Plague vaccine EV, polyoxidonium, betaleukin, erythrocytic antigenic diagnosticum for determination of F1 antibodies and immune reagents for detection of lymphocytes with F1 receptors (LFR) in adhesive test developed by the authors were used. The experiments were carried out in 12 rabbits and 169 guinea pigs.

RESULTS: Immune modulation accelerated the appearance and disappearance of LFR (early phase) and ensured a more rapid and intensive antibody formation (effector phase). Activation by betaleukin is more pronounced than by polyoxidonium. The more rapid and intensive was the development of early phase, the more effective was antibody response to the vaccine. Immune modulation in the experiment with guinea pigs significantly increased protective activity of the vaccine.

CONCLUSION: The use of immune modulators increased immunogenic (in both early and effector phases of antigen-specific response) and protective activity of the EV vaccine. A connection between the acceleration of the first phase of antigen-specific response and general intensity of effector phase of immune response to the EV vaccine was detected. ,}, }
@article {pmid25711027, year = {2014}, author = {Maliarchuk, BA and Derenko, MV and Denisova, GA}, title = {[Episodes of adaptive evolution of mitochondrial genome in Asiatic salamanders (Amphibia, Caudata, Hynobiidae)].}, journal = {Genetika}, volume = {50}, number = {2}, pages = {189-196}, pmid = {25711027}, issn = {0016-6758}, mesh = {Adaptation, Biological/genetics ; Amino Acid Sequence ; Animals ; Base Sequence ; *Evolution, Molecular ; *Genetic Speciation ; Genome, Mitochondrial/*genetics ; Phylogeny ; Selection, Genetic/*genetics ; Urodela/genetics ; }, abstract = {To elucidate the effect of natural selection on the evolution of mitochondrial DNA (mtDNA) in Asiatic salamanders of the family Hynobiidae, nucleotide sequences of 12 protein-coding genes were analyzed. Using a mixed effects model of evolution, it was found that, in spite of the pronounced effect of negative selection on the mtDNA evolution in Hynobiidae (which is typical for the animals in general), two phylogenetic clusters, the West Asian one, represented by the genera Ranodon and Paradactylodon, and North Eurasian one, represented by the genus Salamandrella, were formed under the influence of episodic positive selection. Analysis of protein sequences encoded by the mitochondrial genome also supported the influence of positive selection on the evolution of Hynobiidae at some stages of their cladogenesis. It is suggested that the signatures of adaptive evolution detected in the mtDNA of Hynobiidae were determined by the complex and long-lasting history of their formation, accompanied by adaptation to the changing environment.}, }
@article {pmid25588492, year = {2014}, author = {Soldatskiĭ, IuL and Denisova, OA and Ivanenko, AM}, title = {[The comparative effectiveness of framycetin included in combined therapy of adenoiditis in the children].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {5}, pages = {69-71}, pmid = {25588492}, issn = {0042-4668}, mesh = {Adolescent ; Anti-Infective Agents, Local/administration & dosage/*pharmacology ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Framycetin/administration & dosage/*pharmacology ; Humans ; Male ; Nasal Lavage ; Silver Proteins/administration & dosage/*pharmacology ; Tonsillitis/*drug therapy ; Treatment Outcome ; }, abstract = {The objective of the present study was to evaluate the effectiveness of framycetin included in combined therapy of adenoiditis in the children. The study involved 67 children at the mean age of 6.9±2.7 years. Group 1 was comprised of 35 children given framycetin as topical therapy, the patients of group 2 were treated by the endonasal administration of a 2% silver proteinate solution. It was shown that the use of framycetin as a component of combined therapy of adenoiditis enhances the effectiveness of the treatment and compliance to therapy in comparison with the same parameters in the case of the application of traditional topical antibacterial preparations.}, }
@article {pmid25575941, year = {2015}, author = {Rogers, AR and Bohlender, RJ}, title = {Bias in estimators of archaic admixture.}, journal = {Theoretical population biology}, volume = {100C}, number = {}, pages = {63-78}, doi = {10.1016/j.tpb.2014.12.006}, pmid = {25575941}, issn = {1096-0325}, abstract = {This article evaluates bias in one class of methods used to estimate archaic admixture in modern humans. These methods study the pattern of allele sharing among modern and archaic genomes. They are sensitive to "ghost" admixture, which occurs when a population receives archaic DNA from sources not acknowledged by the statistical model. The effect of ghost admixture depends on two factors: branch-length bias and population-size bias. Branch-length bias occurs because a given amount of admixture has a larger effect if the two populations have been separated for a long time. Population-size bias occurs because differences in population size distort branch lengths in the gene genealogy. In the absence of ghost admixture, these effects are small. They become important, however, in the presence of ghost admixture. Estimators differ in the pattern of response. Increasing a given parameter may inflate one estimator but deflate another. For this reason, comparisons among estimators are informative. Using such comparisons, this article supports previous findings that the archaic population was small and that Europeans received little gene flow from archaic populations other than Neanderthals. It also identifies an inconsistency in estimates of archaic admixture into Melanesia.}, }
@article {pmid25563409, year = {2015}, author = {Perry, GH and Kistler, L and Kelaita, MA and Sams, AJ}, title = {Insights into hominin phenotypic and dietary evolution from ancient DNA sequence data.}, journal = {Journal of human evolution}, volume = {79}, number = {}, pages = {55-63}, doi = {10.1016/j.jhevol.2014.10.018}, pmid = {25563409}, issn = {1095-8606}, mesh = {Animals ; Base Sequence ; *Biological Evolution ; DNA/analysis/genetics ; DNA Copy Number Variations ; Feeding Behavior/*physiology ; Fossils ; Genetic Variation ; Genomics ; Hominidae/*genetics/*physiology ; Humans ; Molecular Sequence Data ; Myosin Heavy Chains/genetics ; Neanderthals ; Paleontology ; Phenotype ; Receptors, G-Protein-Coupled/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Nuclear genome sequence data from Neandertals, Denisovans, and archaic anatomically modern humans can be used to complement our understanding of hominin evolutionary biology and ecology through i) direct inference of archaic hominin phenotypes, ii) indirect inference of those phenotypes by identifying the effects of previously-introgressed alleles still present among modern humans, or iii) determining the evolutionary timing of relevant hominin-specific genetic changes. Here we review and reanalyze published Neandertal and Denisovan genome sequence data to illustrate an example of the third approach. Specifically, we infer the timing of five human gene presence/absence changes that may be related to particular hominin-specific dietary changes and discuss these results in the context of our broader reconstructions of hominin evolutionary ecology. We show that pseudogenizing (gene loss) mutations in the TAS2R62 and TAS2R64 bitter taste receptor genes and the MYH16 masticatory myosin gene occurred after the hominin-chimpanzee divergence but before the divergence of the human and Neandertal/Denisovan lineages. The absence of a functional MYH16 protein may explain our relatively reduced jaw muscles; this gene loss may have followed the adoption of cooking behavior. In contrast, salivary amylase gene (AMY1) duplications were not observed in the Neandertal and Denisovan genomes, suggesting a relatively recent origin for the AMY1 copy number gains that are observed in modern humans. Thus, if earlier hominins were consuming large quantities of starch-rich underground storage organs, as previously hypothesized, then they were likely doing so without the digestive benefits of increased salivary amylase production. Our most surprising result was the observation of a heterozygous mutation in the first codon of the TAS2R38 bitter taste receptor gene in the Neandertal individual, which likely would have resulted in a non-functional protein and inter-individual PTC (phenylthiocarbamide) taste sensitivity variation, as also observed in both humans and chimpanzees.}, }
@article {pmid25556237, year = {2015}, author = {Lin, YL and Pavlidis, P and Karakoc, E and Ajay, J and Gokcumen, O}, title = {The evolution and functional impact of human deletion variants shared with archaic hominin genomes.}, journal = {Molecular biology and evolution}, volume = {32}, number = {4}, pages = {1008-1019}, doi = {10.1093/molbev/msu405}, pmid = {25556237}, issn = {1537-1719}, mesh = {Alleles ; Animals ; *Evolution, Molecular ; Genetic Variation ; *Genome ; Hominidae/*genetics ; Humans ; *Sequence Deletion ; }, abstract = {Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins. However, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. We identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the Human-Neandertal divergence (ancient) and only approximately 9% of which have been introgressed from Neandertals (introgressed). Recurrence, incomplete lineage sorting between human and chimp lineages, and hominid-specific insertions constitute the remaining approximately 4% of allele sharing between humans and archaic hominins. We observed that ancient deletions correspond to more than 13% of all common (>5% allele frequency) deletion variation among modern humans. Our analyses indicate that the genomic landscapes of both ancient and introgressed deletion variants were primarily shaped by purifying selection, eliminating large and exonic variants. We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts. The affected genes are involved in metabolism of external and internal compounds, growth and sperm formation, as well as susceptibility to psoriasis and Crohn's disease. Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection. Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes.}, }
@article {pmid27141645, year = {2015}, author = {Verikovsky, VA and Minakov, OE and Denisova, OI and Bondarenko, EV}, title = {[Results of Investigation of MRSA Susceptibility to Vancomycin in Clinical Units of Large Multifunctional Hospital and Recommendations on Optimization of Antibacterial Therapy of Staphylococcal Infection].}, journal = {Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]}, volume = {60}, number = {11-12}, pages = {35-38}, pmid = {27141645}, issn = {0235-2990}, mesh = {Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Cities ; Drug Resistance, Bacterial ; Hospital Bed Capacity, 500 and over/standards ; Hospitals, District/standards ; Humans ; Methicillin-Resistant Staphylococcus aureus/*drug effects/isolation & purification ; Microbial Sensitivity Tests/methods ; *Practice Guidelines as Topic ; Russia ; Staphylococcal Infections/*drug therapy/epidemiology/microbiology ; Vancomycin/administration & dosage/*therapeutic use ; }, abstract = {The frequency of MRSA and MRSE isolates in various units of the Voronezh Regional Hospital was investigated by the results of the local microbiological monitoring for 2014. The maximum position of MRSA was recorded in the ICU (38 to 75% of the strains). The MRSA strains were characterized by higher methicillin resistance, mainly from the cardiosurgical units (60 to 91% of the isolates). The use of the E-test for MRSA susceptibility to vancomycin allowed to estimate the validity of the use of various antibiotics active against MRSA in the treatment of inpatients and to reduce the risk of ineffective therapy.}, }
@article {pmid27024918, year = {2015}, author = {Slepowa, OS and Svetlova, EV and Kovaleva, LA and Makarov, PV and Kugusheva, AE and Denisova, EV and Vahova, ES and Zaharova, GY and Kondrat'eva, YA and Andryushin, AE and Demkin, VV}, title = {[PCR study of the human herpes virus type 6 and other viruses of the herpes group in eye diseases].}, journal = {Voprosy virusologii}, volume = {60}, number = {6}, pages = {45-48}, pmid = {27024918}, issn = {0507-4088}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anterior Chamber/pathology/virology ; Aqueous Humor/virology ; Child ; Child, Preschool ; Cornea/pathology/virology ; Cytomegalovirus/genetics/isolation & purification ; DNA, Viral/*genetics ; Eye Diseases/*diagnosis/pathology/virology ; Female ; Herpesviridae Infections/*diagnosis/pathology/virology ; Herpesvirus 1, Human/genetics/isolation & purification ; Herpesvirus 2, Human/genetics/isolation & purification ; Herpesvirus 4, Human/genetics/isolation & purification ; Herpesvirus 6, Human/genetics/isolation & purification ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; }, abstract = {To study the role of the HHV-6 type in the development of eye diseases PCR tests of blood (152), cornea biopsies (61), and intraocular fluids (11) for HHV-6 and other viruses of the herpes group (HSV type 1 and 2, CMV, EBV) were conducted. It was found that the HHV-6, along with other representatives of the Herpesviridae, can be detected in patients with different clinical forms of ophthalmopathology (174 patients were surveyed). Viral DNA was detected in blood, cornea, and in the anterior chamber fluid. The obtained data allow that the HHV-6 to be suggested as a possible cause of the ophthalmic herpes along with the other viruses of this group. It makes finding the virus DNA an essential step towards setting the etiologic diagnosis of the ophthalmological patients.}, }
@article {pmid25536760, year = {2014}, author = {Denisova, OI and Davydkin, NF and Kulikov, AG}, title = {[The pathogenetic prerequisites for the application of the general magnetic therapy in the children presenting with cerebral ischemia].}, journal = {Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury}, volume = {}, number = {5}, pages = {56-60}, pmid = {25536760}, issn = {0042-8787}, mesh = {Brain Ischemia/*etiology/physiopathology/*rehabilitation ; Cerebrovascular Circulation/physiology ; Child ; Humans ; Hypoxia, Brain/prevention & control ; *Magnetic Field Therapy ; Microcirculation/physiology ; }, abstract = {This article presents the analysis of the current literature and the original data of the authors providing the rationale for the use of magnetic therapy for the treatment of the children presenting with cerebral ischemia taking into consideration pathogenesis of this disease. It is demonstrated that the application of the general magnetic field decreases the tone of the cerebral vessels and improves blood flow to the brain which increases resistance to cerebral hypoxia. The results of investigations into the microcirculatory changes and liquor dynamics in conjunction with the ventriculometric measurements give evidence of the effectiveness of the combined treatment of cerebral ischemia making use of general magnetic therapy.}, }
@article {pmid25509854, year = {2013}, author = {Maliarchuk, BA}, title = {[Mutation process in the protein-coding genes of human mitochondrial genome in context of evolution of the genus].}, journal = {Molekuliarnaia biologiia}, volume = {47}, number = {6}, pages = {927-933}, pmid = {25509854}, issn = {0026-8984}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Genome, Human/*genetics ; *Genome, Mitochondrial ; Humans ; Mutation/*genetics ; Neanderthals ; Polymorphism, Genetic ; }, abstract = {The human mitochondrial genome, although it has a small size, is characterized by high level of variation, non-uniformly distributed in groups of nucleotide positions that differ in the degree of variability. Considering the mutation process in human mtDNA relative to the mitochondrial genomes of the genus Homo-neandertals, denisova hominin and other primate species, it appears that more than half (56.5%) variable positions in the human mtDNA protein-coding genes are characterized by back (reverse) mutations to the pre-H. sapiens state of mitochondrial genome. It has been found that hypervariable nucleotide positions show a minimal proportion of specific to H. sapiens mutations, and, conversely, a high proportion of mutations (both nucleotide and amino acid substitutions), leading to the loss of Homo-specific variants of polymorphisms. Most often, polymorphisms specific to H. sapiens arise in result of single forward mutations and disappear mainly due to multiple back mutations, including those in the mutational "hotspots".}, }
@article {pmid25487326, year = {2015}, author = {Sánchez-Quinto, F and Lalueza-Fox, C}, title = {Almost 20 years of Neanderthal palaeogenetics: adaptation, admixture, diversity, demography and extinction.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1660}, pages = {20130374}, doi = {10.1098/rstb.2013.0374}, pmid = {25487326}, issn = {1471-2970}, mesh = {Adaptation, Biological/*genetics ; Animals ; *Biological Evolution ; DNA, Mitochondrial/genetics ; *Extinction, Biological ; Fossils ; *Genetic Variation ; Genetics, Population ; Genomics/*methods/trends ; *Hybridization, Genetic ; Neanderthals/*genetics ; Population Dynamics ; }, abstract = {Nearly two decades since the first retrieval of Neanderthal DNA, recent advances in next-generation sequencing technologies have allowed the generation of high-coverage genomes from two archaic hominins, a Neanderthal and a Denisovan, as well as a complete mitochondrial genome from remains which probably represent early members of the Neanderthal lineage. This genomic information, coupled with diversity exome data from several Neanderthal specimens is shedding new light on evolutionary processes such as the genetic basis of Neanderthal and modern human-specific adaptations-including morphological and behavioural traits-as well as the extent and nature of the admixture events between them. An emerging picture is that Neanderthals had a long-term small population size, lived in small and isolated groups and probably practised inbreeding at times. Deleterious genetic effects associated with these demographic factors could have played a role in their extinction. The analysis of DNA from further remains making use of new large-scale hybridization-capture-based methods as well as of new approaches to discriminate contaminant DNA sequences will provide genetic information in spatial and temporal scales that could help clarify the Neanderthal's-and our very own-evolutionary history.}, }
@article {pmid25447821, year = {2015}, author = {Adel, S and Kakularam, KR and Horn, T and Reddanna, P and Kuhn, H and Heydeck, D}, title = {Leukotriene signaling in the extinct human subspecies Homo denisovan and Homo neanderthalensis. Structural and functional comparison with Homo sapiens.}, journal = {Archives of biochemistry and biophysics}, volume = {565}, number = {}, pages = {17-24}, doi = {10.1016/j.abb.2014.10.012}, pmid = {25447821}, issn = {1096-0384}, mesh = {Animals ; Databases, Genetic ; Genome, Human/*physiology ; Humans ; Leukotrienes/*genetics/metabolism ; Lipoxygenases/*genetics/metabolism ; Neanderthals/*genetics/metabolism ; Signal Transduction/*genetics ; Species Specificity ; }, abstract = {Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies.}, }
@article {pmid25403398, year = {2014}, author = {Bugayova, LI and Denisova, TD and Morozova, YA and Sergeeva, SA and Kharlamov, IV}, title = {Effect of afobazole administered to pregnant rats during organogenesis on prenatal development of fetuses.}, journal = {Bulletin of experimental biology and medicine}, volume = {158}, number = {1}, pages = {57-60}, doi = {10.1007/s10517-014-2691-x}, pmid = {25403398}, issn = {1573-8221}, mesh = {Animals ; Anti-Anxiety Agents/therapeutic use/*toxicity ; Benzimidazoles/therapeutic use/*toxicity ; Drug Evaluation, Preclinical ; Female ; Fetal Development/*drug effects ; Male ; Maternal-Fetal Exchange ; Morpholines/therapeutic use/*toxicity ; Organogenesis/*drug effects ; Pregnancy ; Pregnancy Complications/*drug therapy ; Rats ; }, abstract = {Experiments on pregnant rats have demonstrated the absence of damaging effect of Afobazole administered during the antenatal period on organogenesis in fetuses. Afobazole in a dose of 5 mg/kg given to pregnant rats on gestation days 6-16 reduced pre- and post-implantation fetal mortality and improved fertility; 20-day-old embryos had no developmental abnormalities and did not differ from controls by craniocaudal size, body weight, and skeleton ossification. Afobazole in a dose of 100 mg/kg reduced pre- and post-implantation fetal mortality, but had no effect on fertility. No congenital malformations were found in the fetuses, but they were characterized by lower craniocaudal size, body weight, and number of ossification foci in the sternum and spine.}, }
@article {pmid25393762, year = {2014}, author = {Lesecque, Y and Glémin, S and Lartillot, N and Mouchiroud, D and Duret, L}, title = {The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.}, journal = {PLoS genetics}, volume = {10}, number = {11}, pages = {e1004790}, doi = {10.1371/journal.pgen.1004790}, pmid = {25393762}, issn = {1553-7404}, mesh = {Animals ; Chromosomes/genetics ; *Crossing Over, Genetic ; DNA-Binding Proteins ; *Evolution, Molecular ; Gene Conversion ; Genome, Human ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Meiosis/genetics ; Pan troglodytes ; *Recombination, Genetic ; }, abstract = {Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan) to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC), which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.}, }
@article {pmid25301575, year = {2014}, author = {Derenko, M and Malyarchuk, B and Denisova, G and Perkova, M and Litvinov, A and Grzybowski, T and Dambueva, I and Skonieczna, K and Rogalla, U and Tsybovsky, I and Zakharov, I}, title = {Western Eurasian ancestry in modern Siberians based on mitogenomic data.}, journal = {BMC evolutionary biology}, volume = {14}, number = {}, pages = {217}, doi = {10.1186/s12862-014-0217-9}, pmid = {25301575}, issn = {1471-2148}, mesh = {Asian Continental Ancestry Group/genetics ; DNA, Mitochondrial/*genetics ; European Continental Ancestry Group/genetics ; Female ; *Gene Pool ; Genetics, Medical ; *Genetics, Population ; Humans ; Molecular Sequence Data ; Phylogeny ; Phylogeography ; Siberia ; }, abstract = {BACKGROUND: Although the genetic heritage of aboriginal Siberians is mostly of eastern Asian ancestry, a substantial western Eurasian component is observed in the majority of northern Asian populations. Traces of at least two migrations into southern Siberia, one from eastern Europe and the other from western Asia/the Caucasus have been detected previously in mitochondrial gene pools of modern Siberians.

RESULTS: We report here 166 new complete mitochondrial DNA (mtDNA) sequences that allow us to expand and re-analyze the available data sets of western Eurasian lineages found in northern Asian populations, define the phylogenetic status of Siberian-specific subclades and search for links between mtDNA haplotypes/subclades and events of human migrations. From a survey of 158 western Eurasian mtDNA genomes found in Siberia we estimate that nearly 40% of them most likely have western Asian and another 29% European ancestry. It is striking that 65 of northern Asian mitogenomes, i.e. ~41%, fall into 19 branches and subclades which can be considered as Siberian-specific being found so far only in Siberian populations. From the coalescence analysis it is evident that the sequence divergence of Siberian-specific subclades was relatively small, corresponding to only 0.6-9.5 kya (using the complete mtDNA rate) and 1-6 kya (coding region rate).

CONCLUSIONS: The phylogeographic analysis implies that the western Eurasian founders, giving rise to Siberian specific subclades, may trace their ancestry only to the early and mid-Holocene, though some of genetic lineages may trace their ancestry back to the end of Last Glacial Maximum (LGM). We have not found the modern northern Asians to have western Eurasian genetic components of sufficient antiquity to indicate traces of pre-LGM expansions.}, }
@article {pmid25277105, year = {2014}, author = {Schneider, E and El Hajj, N and Haaf, T}, title = {Epigenetic information from ancient DNA provides new insights into human evolution. Commentary on Gokhman D et al. (2014): Reconstructing the DNA methylation maps of the Neanderthal and the Denisovan. Science 344:523-527.}, journal = {Brain, behavior and evolution}, volume = {84}, number = {3}, pages = {169-171}, doi = {10.1159/000365650}, pmid = {25277105}, issn = {1421-9743}, mesh = {Animals ; *DNA Methylation ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Genome, Human ; Humans ; Neanderthals/*genetics ; }, }
@article {pmid25269182, year = {2014}, author = {Cherniaevskaia, GM and Maksimenko, GV and Beloborodova, ÉI and Ustiuzhanina, EA and Denisova, OA}, title = {[Clinical and morphological peculiarities of the clinical course of duodenal ulcer in patients with bronchial asthma].}, journal = {Klinicheskaia meditsina}, volume = {92}, number = {2}, pages = {47-52}, pmid = {25269182}, issn = {0023-2149}, mesh = {Adolescent ; Adult ; Asthma/epidemiology/*pathology ; Comorbidity ; Duodenal Ulcer/epidemiology/etiology/*pathology ; Gastric Mucosa/microbiology/*pathology/physiopathology ; Helicobacter Infections/*complications/epidemiology/pathology ; Helicobacter pylori/*pathogenicity ; Humans ; Inflammation/epidemiology/microbiology/pathology ; Middle Aged ; Prospective Studies ; Young Adult ; }, abstract = {This work was aimed to study clinical features of H. pylori-associated duodenal ulcer (DU) and elucidate morphological features of gastric mucosa (GM) in patients with bronchial asthma (BA). Simultaneous prospective examination of 118 patients aged 18-64 yr included clinical and endoscopic study of the gastroduodenal region with the assessment of gastroenterological symptoms and morphological analysis of GM and duodenal biopsies by histological, histochemical, and morphometric methods. It was shown that GM inflammation in patients with DU and BA is associated not only with H. pylori infection but also with the phase of BA. Structural changes of GM in the patients with DU and BA, unlike those with DU without BA, were apparent not only in the antrum but also in the fundus. Growing density of eosinophil, neutrophil and mast cell infiltration of fundal and antral GM as well as increased total number of cells in the antrum reflects active immune-mediated inflammation in GM lamina propria. It is concluded that negative effect of uncontrolled BA on the clinical course of DU is not restricted to the association of DU exacerbation with the absence of BA control; it is also responsible for enhanced activity of gastritis. One of the possible factors determining combination of H. pylori-associated duodenal ulcer with BA is chronic hyperergic inflammation and marked structural changes in GM.}, }
@article {pmid25265662, year = {2014}, author = {Denisova, OA and Cherniavskaia, GM and Beloborodova, ÉI and Topol'nitskiĭ, EB and Iakimenko, IuV and Chernogoriuk, GÉ and Beloborodova, EV and Strezh, IuA and Vil'danova, LR}, title = {[A case of thoracic actinomycosis].}, journal = {Klinicheskaia meditsina}, volume = {92}, number = {1}, pages = {59-61}, pmid = {25265662}, issn = {0023-2149}, mesh = {Actinomyces/*pathogenicity ; Actinomycosis/*diagnosis/drug therapy/pathology ; Amoxicillin-Potassium Clavulanate Combination/administration & dosage/pharmacology ; Anti-Bacterial Agents/administration & dosage/*pharmacology ; Humans ; Male ; Middle Aged ; Pneumonia, Bacterial/*diagnosis/drug therapy/pathology ; Respiratory Tract Infections/diagnosis/drug therapy/pathology ; Sulbactam/administration & dosage/pharmacology ; Treatment Outcome ; }, abstract = {A case of thoracic actinomycosis manifest as round shadow in the lung is described. Diagnosis was based on the presence of actinomycetes in a transthoracic lung biopsy sample. Treatment for 3 months resulted in recovery. No relapse was documented during 1 year follow-up period.}, }
@article {pmid25257410, year = {2014}, author = {Pinchuk, TV and Fedulaev, YN and Khairetdinova, GA and Denisova, NN and Chura, OV and Logunova, IY}, title = {Anti-inflammatory effects of simvastatin in patients with chronic heart failure.}, journal = {Bulletin of experimental biology and medicine}, volume = {157}, number = {5}, pages = {552-554}, doi = {10.1007/s10517-014-2612-z}, pmid = {25257410}, issn = {1573-8221}, mesh = {Aged ; Anti-Inflammatory Agents/*therapeutic use ; Chronic Disease ; Female ; Heart Failure/*drug therapy ; Humans ; Inflammation Mediators/blood ; Male ; Middle Aged ; Simvastatin/*therapeutic use ; }, abstract = {Proinflammatory markers were evaluated in patients with chronic heart failure of ischemic origin and essential hypertension with preserved left-ventricular ejection fraction before and after a 6-month course of simvastatin therapy (20 mg/day). The study was carried out in 125 patients with diastolic dysfunction manifested as impaired relaxation and pseudonormalization. The main group received standard therapy for chronic heart failure and simvastatin, controls received only standard therapy. In addition, the results in the main group were compared in patients with different types of left-ventricular diastolic dysfunction. Simvastatin therapy significantly reduced the levels of C-reactive protein and IL-6.}, }
@article {pmid25249249, year = {2015}, author = {Kang, L and Michalak, P}, title = {The evolution of cancer-related genes in hominoids.}, journal = {Journal of molecular evolution}, volume = {80}, number = {1}, pages = {37-41}, doi = {10.1007/s00239-014-9649-5}, pmid = {25249249}, issn = {1432-1432}, mesh = {Animals ; Base Sequence ; *Evolution, Molecular ; *Genes, Tumor Suppressor ; Hominidae/*genetics ; Humans ; *Oncogenes ; Sequence Homology, Nucleic Acid ; }, abstract = {The evolution of cancer suppression is essential for the maintenance of multicellularity. The lack of correlation between body size and cancer risk across species, known as Peto's paradox, suggests that genetic variation in cancer resistance is sufficient to compensate for increases of cell numbers in bigger animals. To assess evolutionary dynamics of cancer-related genes, we analyzed Ka, Ks,and Ka/Ks values in 120 oncogenes and tumor suppressor genes (TSG) among seven hominoid species, including two extinct species, Neanderthal and Denisovan. Ka/Ks of tumor suppressor genes tended to be higher relative to that of oncogenes, consistent with relaxed purifying selection acting on the former. Ka/Ks values were positively correlated with TSG scores, but negatively correlated with oncogene scores, suggesting opposing selection pressures operating on the two groups of cancer-related genes. Additionally, we found 108 species-divergent substitutions that were prevalent germline genotypes in some species but in humans appeared only as somatic cancerous mutations. Better understanding the resistance to cancer may lead to new methods of cancer prevention in humans.}, }
@article {pmid25172957, year = {2014}, author = {Racimo, F and Kuhlwilm, M and Slatkin, M}, title = {A test for ancient selective sweeps and an application to candidate sites in modern humans.}, journal = {Molecular biology and evolution}, volume = {31}, number = {12}, pages = {3344-3358}, doi = {10.1093/molbev/msu255}, pmid = {25172957}, issn = {1537-1719}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; R01-GM40282/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; *Evolution, Molecular ; Genome, Human ; Humans ; *Models, Genetic ; Neanderthals/genetics ; Polymorphism, Single Nucleotide ; Selection, Genetic ; }, abstract = {We introduce a new method to detect ancient selective sweeps centered on a candidate site. We explored different patterns produced by sweeps around a fixed beneficial mutation, and found that a particularly informative statistic measures the consistency between majority haplotypes near the mutation and genotypic data from a closely related population. We incorporated this statistic into an approximate Bayesian computation (ABC) method that tests for sweeps at a candidate site. We applied this method to simulated data and show that it has some power to detect sweeps that occurred more than 10,000 generations in the past. We also applied it to 1,000 Genomes and Complete Genomics data combined with high-coverage Denisovan and Neanderthal genomes to test for sweeps in modern humans since the separation from the Neanderthal-Denisovan ancestor. We tested sites at which humans are fixed for the derived (i.e., nonchimpanzee allele) whereas the Neanderthal and Denisovan genomes are homozygous for the ancestral allele. We observe only weak differences in statistics indicative of selection between functional categories. When we compare patterns of scaled diversity or use our ABC approach, we fail to find a significant difference in signals of classic selective sweeps between regions surrounding nonsynonymous and synonymous changes, but we detect a slight enrichment for reduced scaled diversity around splice site changes. We also present a list of candidate sites that show high probability of having undergone a classic sweep in the modern human lineage since the split from Neanderthals and Denisovans.}, }
@article {pmid25142605, year = {2014}, author = {Lee, A and Huntley, D and Aiewsakun, P and Kanda, RK and Lynn, C and Tristem, M}, title = {Novel Denisovan and Neanderthal retroviruses.}, journal = {Journal of virology}, volume = {88}, number = {21}, pages = {12907-12909}, doi = {10.1128/JVI.01825-14}, pmid = {25142605}, issn = {1098-5514}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Endogenous Retroviruses/classification/*genetics/*isolation & purification ; Female ; Fossils/*virology ; Genome ; Hominidae/*virology ; }, abstract = {Following the recent availability of high-coverage genomes for Denisovan and Neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported HERV-K(HML2) elements (HERV-K is human endogenous retrovirus K). These elements are absent from the human genome (hg38) and appear to be unique to archaic hominids. These findings provide further evidence supporting the recent activity of the HERV-K(HML2) group, which has been implicated in human disease. They will also provide insights into the evolution of archaic hominids.}, }
@article {pmid25110108, year = {2014}, author = {Malyarchuk, B and Derenko, M and Denisova, G}, title = {A mitogenomic phylogeny and genetic history of sable (Martes zibellina).}, journal = {Gene}, volume = {550}, number = {1}, pages = {56-67}, doi = {10.1016/j.gene.2014.08.015}, pmid = {25110108}, issn = {1879-0038}, mesh = {Animals ; Asia ; Bayes Theorem ; Cytochromes b/genetics ; DNA, Mitochondrial/chemistry/classification/*genetics ; Europe ; Evolution, Molecular ; Genetic Variation ; Genetics, Population ; Genome, Mitochondrial/*genetics ; Geography ; Molecular Sequence Data ; Mustelidae/*genetics ; NADH Dehydrogenase/genetics ; *Phylogeny ; Selection, Genetic ; Sequence Analysis, DNA ; Time Factors ; }, abstract = {We assessed phylogeny of sable (Martes zibellina, Linnaeus, 1758) by sequence analysis of nearly complete, new mitochondrial genomes in 36 specimens from different localities in northern Eurasia (Primorye, Khabarovsk and Krasnoyarsk regions, the Kamchatka Peninsula, the Kuril Islands and the Urals). Phylogenetic analysis of mtDNA sequences demonstrates that two clades, A and BC, radiated about 200-300 thousandyears ago (kya) according to results of Bayesian molecular clock and RelTime analyses of different mitogenome alignments (nearly complete mtDNA sequences, protein-coding region, and synonymous sites), while the age estimates of clades A, B and C fall within the Late Pleistocene (~50-140 kya). Bayesian skyline plots (BSPs) of sable population size change based on analysis of nearly complete mtDNAs show an expansion around 40 kya in the warm Karganian time, without a decline of population size around the Last Glacial Maximum (21 kya). The BSPs based on synonymous clock rate indicate that M. zibellina experienced demographic expansions later, approximately 22 kya. The A2a clade that colonized Kamchatka ~23-50 kya (depending on the mutation rate used) survived the last glaciation there as demonstrated by the BSP analysis. In addition, we have found evidence of positive selection acting at ND4 and cytochrome b genes, thereby suggesting adaptive evolution of the A2a clade in Kamchatka.}, }
@article {pmid25073341, year = {2014}, author = {Petrov, AG and Denisova, SV and Odintseva, OV and Raudina, SN}, title = {[Methodologic approaches to farmacologic economic analysis of actual inpatient treatment of occupational diseases].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {2}, pages = {42-45}, pmid = {25073341}, issn = {1026-9428}, mesh = {Hearing Loss, Sensorineural/drug therapy/economics ; *Hospitalization/economics/statistics & numerical data ; Humans ; Models, Statistical ; *Occupational Diseases/drug therapy/economics ; }, abstract = {To improve miners' health nowadays, effective application of available means and implication of economic management methods are necessary, as quality medical and pharmaceutic care for miners requires significant financial, material and working efforts both from the government and from every institution operating in health care.}, }
@article {pmid25051667, year = {2014}, author = {Katamanova, EV and Shevchenko, OI and Lakhman, OL and Denisova, IA}, title = {[Cognitive disorders in patients with chronic mercury intoxication].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {4}, pages = {7-12}, pmid = {25051667}, issn = {1026-9428}, mesh = {Cognition Disorders/classification/etiology/*physiopathology ; Humans ; Male ; Mercury Poisoning, Nervous System/complications/*physiopathology ; Middle Aged ; Occupational Diseases/chemically induced/*physiopathology ; Occupational Exposure/*adverse effects ; Severity of Illness Index ; }, abstract = {To assess severity of cognitive disorders in chronic mercury intoxication, the authors performed claster and discrimination analysis of neuropsychologic and neurophysiologic research data from workers exposed to mercury during long length of service, from patients with early and marked stages of chronic mercurial intoxication. Cognitive disorders in chronic mercurial intoxication have three severity degrees, in the light degree disorders patients demonstrate lower amplitude of cognitive evoked potentials, poor long-term memory and associative thinking. Moderate cognitive disorders are characterized by decreased visual, long-term memory, concentration of attention, poor optic and spatial gnosis. Marked cognitive disorders with chronic mercurial intoxication present with more decreased long-term, short-term, picturesque memory, poor intellect, optic and spatial gnosis and associative thinking.}, }
@article {pmid25043523, year = {2014}, author = {Jorner, K and Emanuelsson, R and Dahlstrand, C and Tong, H and Denisova, AV and Ottosson, H}, title = {Impact of ground- and excited-state aromaticity on cyclopentadiene and silole excitation energies and excited-state polarities.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {20}, number = {30}, pages = {9295-9303}, doi = {10.1002/chem.201402577}, pmid = {25043523}, issn = {1521-3765}, abstract = {A new qualitative model for estimating the properties of substituted cyclopentadienes and siloles in their lowest ππ* excited states is introduced and confirmed through quantum chemical calculations, and then applied to explain earlier reported experimental excitation energies. According to our model, which is based on excited-state aromaticity and antiaromaticity, siloles and cyclopentadienes are cross-hyperconjugated "aromatic chameleons" that adapt their electronic structures to conform to the various aromaticity rules in different electronic states (Hückel's rule in the π(2) electronic ground state (S0) and Baird's rule in the lowest ππ* excited singlet and triplet states (S1 and T1)). By using pen-and-paper arguments, one can explain polarity changes upon excitation of substituted cyclopentadienes and siloles, and one can tune their lowest excitation energies by combined considerations of ground- and excited-state aromaticity/antiaromaticity effects. Finally, the "aromatic chameleon" model can be extended to other monocyclic compound classes of potential use in organic electronics, thereby providing a unified view of the S0, T1, and S1 states of a range of different cyclic cross-π-conjugated and cross-hyperconjugated compound classes.}, }
@article {pmid25043035, year = {2014}, author = {Huerta-Sánchez, E and Jin, X and Asan, and Bianba, Z and Peter, BM and Vinckenbosch, N and Liang, Y and Yi, X and He, M and Somel, M and Ni, P and Wang, B and Ou, X and Huasang, and Luosang, J and Cuo, ZX and Li, K and Gao, G and Yin, Y and Wang, W and Zhang, X and Xu, X and Yang, H and Li, Y and Wang, J and Wang, J and Nielsen, R}, title = {Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA.}, journal = {Nature}, volume = {512}, number = {7513}, pages = {194-197}, doi = {10.1038/nature13408}, pmid = {25043035}, issn = {1476-4687}, support = {R01 HG003229/HG/NHGRI NIH HHS/United States ; R01HG003229/HG/NHGRI NIH HHS/United States ; R01HG003229-08S2/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; *Altitude ; Animals ; Asian Continental Ancestry Group/genetics ; Basic Helix-Loop-Helix Transcription Factors/genetics ; DNA/*genetics ; Gene Frequency ; *Genetic Variation ; Haplotypes ; Hominidae/*genetics ; Humans ; Polymorphism, Single Nucleotide ; Tibet ; }, abstract = {As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.}, }
@article {pmid25001002, year = {2014}, author = {Schwartz, JJ and Roach, DJ and Thomas, JH and Shendure, J}, title = {Primate evolution of the recombination regulator PRDM9.}, journal = {Nature communications}, volume = {5}, number = {}, pages = {4370}, doi = {10.1038/ncomms5370}, pmid = {25001002}, issn = {2041-1723}, support = {R01 HG006283/HG/NHGRI NIH HHS/United States ; HG006283/HG/NHGRI NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *Evolution, Molecular ; Genetic Variation ; Histone-Lysine N-Methyltransferase/*genetics ; Molecular Sequence Data ; Primates/*genetics ; Selection, Genetic ; Sequence Analysis, DNA ; Zinc Fingers ; }, abstract = {The PRDM9 gene encodes a protein with a highly variable tandem-repeat zinc finger (ZF) DNA-binding domain that plays a key role in determining sequence-specific hotspots of meiotic recombination genome wide. Here we survey the diversity of the PRDM9 ZF domain by sequencing this region in 64 primates from 18 species, revealing 68 unique alleles across all groups. We report ubiquitous positive selection at nucleotide positions corresponding to DNA contact residues and the expansion of ZFs within clades, which confirms the rapid evolution of the ZF domain throughout the primate lineage. Alignment of Neandertal and Denisovan sequences suggests that PRDM9 in archaic hominins was closely related to present-day human alleles that are rare and specific to African populations. In the context of its role in reproduction, our results are consistent with variation in PRDM9 contributing to speciation events in primates.}, }
@article {pmid24845746, year = {2014}, author = {Denisova, K and Kibbe, MM and Cholewiak, SA and Kim, SH}, title = {Intra- and intermanual curvature aftereffect can be obtained via tool-touch.}, journal = {IEEE transactions on haptics}, volume = {7}, number = {1}, pages = {61-66}, doi = {10.1109/TOH.2013.63}, pmid = {24845746}, issn = {2329-4051}, mesh = {Adult ; Feedback, Sensory/*physiology ; Female ; Humans ; Male ; Space Perception/*physiology ; Touch Perception/*physiology ; }, abstract = {We examined the perception of virtual curved surfaces explored with a tool. We found a reliable curvature aftereffect, suggesting neural representation of the curvature in the absence of direct touch. Intermanual transfer of the aftereffect suggests that this representation is somewhat independent of the hand used to explore the surface.}, }
@article {pmid24832686, year = {2014}, author = {Wong, LP and Lai, JK and Saw, WY and Ong, RT and Cheng, AY and Pillai, NE and Liu, X and Xu, W and Chen, P and Foo, JN and Tan, LW and Koo, SH and Soong, R and Wenk, MR and Lim, WY and Khor, CC and Little, P and Chia, KS and Teo, YY}, title = {Insights into the genetic structure and diversity of 38 South Asian Indians from deep whole-genome sequencing.}, journal = {PLoS genetics}, volume = {10}, number = {5}, pages = {e1004377}, doi = {10.1371/journal.pgen.1004377}, pmid = {24832686}, issn = {1553-7404}, mesh = {*Genetic Variation ; *Genetics, Population ; *Genome, Human ; Haplotypes ; Humans ; India ; Polymorphism, Single Nucleotide ; }, abstract = {South Asia possesses a significant amount of genetic diversity due to considerable intergroup differences in culture and language. There have been numerous reports on the genetic structure of Asian Indians, although these have mostly relied on genotyping microarrays or targeted sequencing of the mitochondria and Y chromosomes. Asian Indians in Singapore are primarily descendants of immigrants from Dravidian-language-speaking states in south India, and 38 individuals from the general population underwent deep whole-genome sequencing with a target coverage of 30X as part of the Singapore Sequencing Indian Project (SSIP). The genetic structure and diversity of these samples were compared against samples from the Singapore Sequencing Malay Project and populations in Phase 1 of the 1,000 Genomes Project (1 KGP). SSIP samples exhibited greater intra-population genetic diversity and possessed higher heterozygous-to-homozygous genotype ratio than other Asian populations. When compared against a panel of well-defined Asian Indians, the genetic makeup of the SSIP samples was closely related to South Indians. However, even though the SSIP samples clustered distinctly from the Europeans in the global population structure analysis with autosomal SNPs, eight samples were assigned to mitochondrial haplogroups that were predominantly present in Europeans and possessed higher European admixture than the remaining samples. An analysis of the relative relatedness between SSIP with two archaic hominins (Denisovan, Neanderthal) identified higher ancient admixture in East Asian populations than in SSIP. The data resource for these samples is publicly available and is expected to serve as a valuable complement to the South Asian samples in Phase 3 of 1 KGP.}, }
@article {pmid24786081, year = {2014}, author = {Gokhman, D and Lavi, E and Prüfer, K and Fraga, MF and Riancho, JA and Kelso, J and Pääbo, S and Meshorer, E and Carmel, L}, title = {Reconstructing the DNA methylation maps of the Neandertal and the Denisovan.}, journal = {Science (New York, N.Y.)}, volume = {344}, number = {6183}, pages = {523-527}, doi = {10.1126/science.1250368}, pmid = {24786081}, issn = {1095-9203}, mesh = {Animals ; *DNA Methylation ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Genome, Human ; Humans ; Neanderthals/*genetics ; }, abstract = {Ancient DNA sequencing has recently provided high-coverage archaic human genomes. However, the evolution of epigenetic regulation along the human lineage remains largely unexplored. We reconstructed the full DNA methylation maps of the Neandertal and the Denisovan by harnessing the natural degradation processes of methylated and unmethylated cytosines. Comparing these ancient methylation maps to those of present-day humans, we identified ~2000 differentially methylated regions (DMRs). Particularly, we found substantial methylation changes in the HOXD cluster that may explain anatomical differences between archaic and present-day humans. Additionally, we found that DMRs are significantly more likely to be associated with diseases. This study provides insight into the epigenetic landscape of our closest evolutionary relatives and opens a window to explore the epigenomes of extinct species.}, }
@article {pmid24752266, year = {2014}, author = {Denisova, OV and Söderholm, S and Virtanen, S and Von Schantz, C and Bychkov, D and Vashchinkina, E and Desloovere, J and Tynell, J and Ikonen, N and Theisen, LL and Nyman, TA and Matikainen, S and Kallioniemi, O and Julkunen, I and Muller, CP and Saelens, X and Verkhusha, VV and Kainov, DE}, title = {Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.}, journal = {Antimicrobial agents and chemotherapy}, volume = {58}, number = {7}, pages = {3689-3696}, doi = {10.1128/AAC.02798-13}, pmid = {24752266}, issn = {1098-6596}, mesh = {Cell Line ; Cytokines/metabolism ; Heterocyclic Compounds, 3-Ring/*pharmacology ; Host-Pathogen Interactions/drug effects ; Humans ; In Vitro Techniques ; *Influenza A Virus, H1N1 Subtype ; Influenza, Human/*prevention & control/virology ; Molecular Sequence Data ; Oncogene Protein v-akt/*antagonists & inhibitors ; Phosphoproteins/metabolism ; Protease Inhibitors/*pharmacology ; RNA, Small Interfering/genetics ; Transfection ; Viral Plaque Assay ; }, abstract = {The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.}, }
@article {pmid24667833, year = {2014}, author = {Sazzini, M and Schiavo, G and De Fanti, S and Martelli, PL and Casadio, R and Luiselli, D}, title = {Searching for signatures of cold adaptations in modern and archaic humans: hints from the brown adipose tissue genes.}, journal = {Heredity}, volume = {113}, number = {3}, pages = {259-267}, doi = {10.1038/hdy.2014.24}, pmid = {24667833}, issn = {1365-2540}, mesh = {Adaptation, Physiological/*genetics ; Adipose Tissue, Brown/*metabolism ; Alleles ; Biological Evolution ; Climate ; Cold Temperature ; Fossils ; Genome/*genetics ; Humans/*genetics ; Thermogenesis/*genetics ; }, abstract = {Adaptation to low temperatures has been reasonably developed in the human species during the colonization of the Eurasian landmass subsequent to Out of Africa migrations of anatomically modern humans. In addition to morphological and cultural changes, also metabolic ones are supposed to have favored human isolation from cold and body heat production and this can be hypothesized also for most Neandertal and at least for some Denisovan populations, which lived in geographical areas that strongly experienced the last glacial period. Modulation of non-shivering thermogenesis, for which adipocytes belonging to the brown adipose tissue are the most specialized cells, might have driven these metabolic adaptations. To perform an exploratory analysis aimed at looking into this hypothesis, variation at 28 genes involved in such functional pathway was investigated in modern populations from different climate zones, as well as in Neandertal and Denisovan genomes. Patterns of variation at the LEPR gene, strongly related to increased heat dissipation by mitochondria, appeared to have been shaped by positive selection in modern East Asians, but not in Europeans. Moreover, a single potentially cold-adapted LEPR allele, different from the supposed adaptive one identified in Homo sapiens, was found also in Neandertal and Denisovan genomes. These findings suggest that independent mechanisms for cold adaptations might have been developed in different non-African human groups, as well as that the evolution of possible enhanced thermal efficiency in Neandertals and in some Denisovan populations has plausibly entailed significant changes also in other functional pathways than in the examined one.}, }
@article {pmid24599118, year = {2014}, author = {Mariotti, M and Smith, TF and Sudmant, PH and Goldberger, G}, title = {Pseudogenization of testis-specific Lfg5 predates human/Neanderthal divergence.}, journal = {Journal of human genetics}, volume = {59}, number = {5}, pages = {288-291}, doi = {10.1038/jhg.2014.6}, pmid = {24599118}, issn = {1435-232X}, mesh = {Animals ; *Evolution, Molecular ; Exons ; Genomics ; Humans ; Introns ; Male ; Multigene Family ; Mutation ; Neanderthals/*genetics ; Organ Specificity/*genetics ; Phylogeny ; Testis/*metabolism ; }, abstract = {Recent reviews discussed the critical roles of apoptosis in human spermatogenesis and infertility. These reviews highlight the FasL-induced caspase cascade in apoptosis lending importance to our discovery of the pseudogene status of the Lfg5 gene in modern humans, Neanderthal and the Denisovan. This gene is a member of the ancient and highly conserved apoptosis Lifeguard family. This pseudogenization is the result of a premature stop codon at the 3'-end of exon 8 not found in any other ortholog. With the current exception of the domesticated bovine and buffalo, Lfg5's expression in mammals is testis-specific. A full analysis of this gene, its phylogenetic context and its recent hominin changes suggest its inactivation was likely under selection in human evolution.}, }
@article {pmid24501955, year = {2013}, author = {Agafonova, EV and Malanicheva, TG and Denisova, SN}, title = {[Subpopulations and phagocytic activity of monocytes in chronic gastroduodenitis in children].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {5}, pages = {108-111}, pmid = {24501955}, issn = {1682-8658}, mesh = {Adolescent ; Candida/*immunology ; Candidiasis/*immunology ; Child ; Child, Preschool ; Duodenitis/*immunology ; Female ; Gastritis/*immunology ; Helicobacter Infections ; Helicobacter pylori/*immunology ; Humans ; Male ; Monocytes/*immunology ; Phagocytosis/*immunology ; }, abstract = {There was conducted a study of the phagocytic activity, immunophenotype and peripheral blood monocytes by flow cytometry in children with chronic gastroduodenitis associated with Helicobacter pylori, as well as the association of Helicobacter pylori with fungi of the genus Candida and markers of secondary immune deficiency. The differential changes in the structure of circulating profile of monocytes were revealed, that indicate the pathogenetic significance of these disorders in chronic gastroduodenitis with H. pylori etiology, as well as at association of Helicobacter pylori with fungi of the genus Candida. Violations of the phagocytic activity of monocytes in chronic gastroduodenitis in children are associated with depression of different stages of phagocytosis--capture functions, mobilization, killing, intracellular biocidity. A severe depression in phagocytic activity of monocytes occurs in CGD associated with Hp and fungi of the genus Candida.}, }
@article {pmid24450152, year = {2013}, author = {Malyarchuk, BA and Denisova, GA and Derenko, MV}, title = {[Peculiarities of phosphoglycerate kinase-1 pseudogene evolution in Schrenck salamander (Salamandrella schrenckii Strauch, 1870)].}, journal = {Genetika}, volume = {49}, number = {7}, pages = {830-837}, pmid = {24450152}, issn = {0016-6758}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Molecular Sequence Data ; Phosphoglycerate Kinase/*genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Pseudogenes/*genetics ; Urodela/*genetics ; }, abstract = {Processed copies of genes generally evolve in neutral mode as pseudogenes, however, some of them might be important sources of new functional genes. The psiPGK1 pseudogene has been discovered in Schrenck salamander (Salamandrella schrenckii, Amphibia, Caudata, Hynobiidae) via polymerase chain reaction used to amplify the phosphoglycerate kinase 1 gene (PGK1). This pseudogene is an intronless copy of PGK1 gene absent of exon 6. Analysis of psiPGK1 pseudogene polymorphism has demonstrated that it lacks mutations, which results in shifts in the stop codons and reading frames, as well as that the interspecies variation of this pseudogene was inconsistent with the neutral model of evolution. In addition, the pattern of phylogeographic differentiation of the psiPGK1 variants mainly coincides with that observed in mitochondrial DNA. These observations allow it to be suggested that the psiPGK1 pseudogene is a new functional gene in the Schrenck salamander.}, }
@article {pmid24392153, year = {2014}, author = {Hughes, GM and Teeling, EC and Higgins, DG}, title = {Loss of olfactory receptor function in hominin evolution.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e84714}, doi = {10.1371/journal.pone.0084714}, pmid = {24392153}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Databases, Nucleic Acid ; Evolution, Molecular ; Genome ; Genomics ; Hominidae/*genetics ; Humans ; Molecular Sequence Data ; Multigene Family ; Olfactory Receptor Neurons/*metabolism ; Phylogeny ; Receptors, Odorant/chemistry/classification/*genetics ; Sequence Alignment ; }, abstract = {The mammalian sense of smell is governed by the largest gene family, which encodes the olfactory receptors (ORs). The gain and loss of OR genes is typically correlated with adaptations to various ecological niches. Modern humans have 853 OR genes but 55% of these have lost their function. Here we show evidence of additional OR loss of function in the Neanderthal and Denisovan hominin genomes using comparative genomic methodologies. Ten Neanderthal and 8 Denisovan ORs show evidence of loss of function that differ from the reference modern human OR genome. Some of these losses are also present in a subset of modern humans, while some are unique to each lineage. Morphological changes in the cranium of Neanderthals suggest different sensory arrangements to that of modern humans. We identify differences in functional olfactory receptor genes among modern humans, Neanderthals and Denisovans, suggesting varied loss of function across all three taxa and we highlight the utility of using genomic information to elucidate the sensory niches of extinct species.}, }
@article {pmid25929022, year = {2014}, author = {Pogozheva, AV and Sorokina, EY and Baturin, AK and Peskova, EV and Makurina, ON and Levin, LG and Soto, SKh and Aristarkhova, TA and Korosteleva, MM and Denisova, NN and Solntseva, TN and Aleshina, IV and Toboleva, MA and Redzyuk, LA and Polyakova, AV}, title = {[The role of the Consultative and Diagnostic Centre "Healthy Nutrition" in the diagnosis and nutritional prevention of non-communicable diseases].}, journal = {Voprosy pitaniia}, volume = {83}, number = {6}, pages = {52-57}, pmid = {25929022}, issn = {0042-8833}, mesh = {Body Mass Index ; Diabetes Mellitus, Type 2/blood/*diagnosis/genetics/*prevention & control ; Energy Intake ; Female ; Humans ; Male ; *Nutritional Status ; Obesity/blood/*diagnosis/genetics/*prevention & control ; Polymorphism, Genetic ; }, abstract = {In a consultative and diagnostic center "Healthy Nutrition" of Institute of Nutrition the nutritional status of 3500 patients (mean age 48.4 ± 0.3 years) liv- ing in the Moscow region, using a system Nutritest IP-3, including genomic analysis has been examined. In the analysis of dietary intake by an average review, increased energy intake due to excess intake of the total (44.2% energy) and saturated fat (13.6%) has been shown. 30.0% of patients were overweight and 34.1% were obese. Osteopenia was detected in 31.0% of men and 25.0% women, osteoporosis--20.9% and 30.3%, respectively. Analysis of the results of biochemical studies revealed increased cholesterol in 68.7% of patients, LDL cholesterol--at 63.9%, triglycerides-- at 22.5%, glucose--at 29.4%. The frequency of the occurrence of risk alleles of genes associated with the development of obesity and type 2 diabetes mellitus was: 47.8%--for the polymorphism rs9939609 (FTO gene), 8.3%--for polymorphism rs4994 (gene ADRB3), 60.2%--for the polymorphism rs659366 (gene UCP2), 36.6%--for the rs5219 polymorphism in the gene of ATP-dependent potassium channel.}, }
@article {pmid25845144, year = {2014}, author = {Isaeva, NA and Torubarov, FS and Denisova, EA and Zvereva, ZF and Koronotova, MA}, title = {[Evaluating psychophysiologic adaptation state in operators of Bilibino nuclear power station].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {11}, pages = {16-20}, pmid = {25845144}, issn = {1026-9428}, mesh = {Adaptation, Physiological/*physiology ; Adaptation, Psychological/*physiology ; Adult ; Humans ; Middle Aged ; Neuropsychological Tests ; *Nuclear Power Plants ; Occupational Diseases/epidemiology/*physiopathology/psychology ; Occupational Exposure/analysis ; Psychophysiologic Disorders/epidemiology/*physiopathology/psychology ; Russia ; }, abstract = {The study revealed that 60% operators of Bilibino nuclear power station suffer from psychosomatic diseases, 41.7% of them are assigned to occupational group of workers, and major part of the examinees with psychosomatic diseases (45.82%) are aged 41-50, high integral level ofpsychophysiologic adaptation is revealed in 5 examinees (12.5%), medium integral level--in 12 examinees (30%). Lower integral level of psychophysiologic adaptation manifested in decrease in psychophysiologic and physiologic levels.}, }
@article {pmid25816630, year = {2014}, author = {Shostak, NA and Muradiants, AA and Kondrashov, AA and Denisova, SN}, title = {[Clinical efficacy instant goat milk in the complex therapy and prevention of osteoporosis in patients with rheumatoid arthritis].}, journal = {Voprosy pitaniia}, volume = {83}, number = {5}, pages = {79-85}, pmid = {25816630}, issn = {0042-8833}, mesh = {Animals ; Arthritis, Rheumatoid/*blood/*prevention & control ; Calcifediol/blood ; Calcitriol/blood ; Calcium/blood ; Female ; *Goats ; Humans ; Male ; Middle Aged ; *Milk ; Osteoporosis, Postmenopausal/*blood/*prevention & control ; Phosphorus/blood ; }, abstract = {Osteoporosis (OP) in rheumatoid arthritis (RA) refers to a secondary immune-mediated metabolic osteopathy characterized by periarticular and systemic decreased bone mass, impaired bone strength and increased risk of fractures. According to some studies, adding milk in the diet helps to increase bone mineral density and to reduce the risk of osteoporosis and maintain normal levels of vitamin D. To study the state of mineral and bone metabolism in RA patients zeith osteopenic syndrome and to evaluate the effectiveness of treatment and prevention of OP by adding dry goat milk "Amalteya" in the diet. The study included 42 patients with a documented diagnosis of RA (ACR, 1987) - 23 men (mean age 59 years) and 19 postmenopausal women (mean age 62 years) with the presence of osteoporosis and osteopenia according to the dual-energy X-ray absorptiometry. 21 (50%) RA patients (main group) received standard antiosteoporotichesky (alendronate 70 mg/week + calcium 1000 mg/day + Vitamin D3 800 IU/day) therapy and milk powder Amalteya® (400 ml/day). The control group (21 patients with RA) received only standard antiosteoporotic therapy. Follow-up lasted for 6 months. The concentration of total calcium in the blood of RA patients was on average 2.33 mmol/l, ionized Ca - 1,18 mmol/l and inorganic P - 1,09 mmol/l, which corresponds to normal values. Vitamin D deficiency was found in 17,5% of patients, and failure - in 32,5% of patients with RA. After 6 months of the treatment it was found that b-CrossLaps levels tend to be reducing in both of the groups and with reduction of bone formation marker osteocalcin in the group not receiving goat milk. Also, due to the background of ongoing combinative therapy it was clear that concentrations of 1,25(OH)2D and 25(OH)D in the blood serum are increasing (by 18,5-28,2% at the main group and by 8,0-17,9% at the control group), however, inter-group differences was below the level of the reliable importance. It was strongly marked in the group who received goat's milk "Amalteya®". Reduced levels of vitamin D in the blood is typical for 50% of RA patients with osteopenic syndrome with normal values of calcium-phosphorus metabolism. Combination therapy and prevention of osteoporosis in patients with RA with an additional inclusion in the diet of the daily administration of 400 ml of goat's milk Amalthea® has a positive impact on bone metabolism.}, }
@article {pmid25799827, year = {2014}, author = {Vizel', IIu and Shmelev, EI and Baranova, OP and Barlamov, PN and Borodina, GL and Denisova, OA and Dobin, VL and Kulbaisov, AM and Kupaev, VI and Listopadova, MV and Ovsiannikov, NV and Os'kin, DN and Petrov, DV and Solov'ev, KI and Shul'zhenko, LV and Vizel', AA}, title = {[Multicenter retrospective analysis of the patients with sarcoidosis with a 10 year interval in observations].}, journal = {Klinicheskaia meditsina}, volume = {92}, number = {6}, pages = {28-34}, pmid = {25799827}, issn = {0023-2149}, mesh = {Adult ; Antitubercular Agents/*therapeutic use ; Disease-Free Survival ; Female ; Glucocorticoids/*therapeutic use ; Humans ; Lung/diagnostic imaging ; Male ; Patient Acuity ; Prognosis ; Radiography ; Recurrence ; Respiratory Function Tests/methods ; Risk Factors ; Russia/epidemiology ; *Sarcoidosis/diagnosis/epidemiology/physiopathology/therapy ; }, abstract = {Comparison of the state of 83 patients with histologically confirmed sarcoidosis observed with a 10 year interval revealed remission in 47% of the cases. The main factors having negative effect on prognosis of the disease included extrapulmonary symptoms, the use ofcorticosteroids (at all stages, especially at stage I and in Lofgren syndrome) and antituberculosis drugs, positive TB test. Risk factors of relapses were stage II sarcoidosis, the use of systemic corticosteroids in patients with Lofgren syndrome and antituberculosis drugs, initially low FEV1/FVLC ratio and the number of lymphocytes in peripheral blood.}, }
@article {pmid25734313, year = {2014}, author = {Mazur, EM and Soldatskiĭ, IL and Ivanenko, AM and Denisova, OA and Severin, TV}, title = {[Foreign bodies (disk batteries) in the nose].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {6}, pages = {64-65}, pmid = {25734313}, issn = {0042-4668}, mesh = {Child, Preschool ; Electric Power Supplies/*adverse effects ; Female ; *Foreign Bodies ; Humans ; Male ; Nose/*injuries ; }, abstract = {This paper reports the results of analysis of the treatment of 8 children after the removal a disk battery from the nasal cavity. It was shown that the restoration of all the structures of the nasal cavity is possible if the foreign body remains in it during a short (up to 5 hours) time. The longer presence of such a body in the nasal cavity gives rise to post-traumatic defects, in the first place septal perforations and injuries to the inferior turbinated bone. In such cases, the foreign body must be immediately removed from the nasal cavity, and the child should be placed under thorough medical observation taking into consideration the long process of rejection of necrotic tissues and healing of the resulting defects.}, }
@article {pmid24367647, year = {2013}, author = {Reno, PL and McLean, CY and Hines, JE and Capellini, TD and Bejerano, G and Kingsley, DM}, title = {A penile spine/vibrissa enhancer sequence is missing in modern and extinct humans but is retained in multiple primates with penile spines and sensory vibrissae.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e84258}, doi = {10.1371/journal.pone.0084258}, pmid = {24367647}, issn = {1932-6203}, support = {RR016483/RR/NCRR NIH HHS/United States ; RR014491/RR/NCRR NIH HHS/United States ; 5P50HG2568/HG/NHGRI NIH HHS/United States ; RR015087/RR/NCRR NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Enhancer Elements, Genetic/*genetics ; *Extinction, Biological ; Genome, Human/genetics ; Humans ; Male ; Molecular Sequence Data ; Penis/*metabolism ; Primates/*genetics ; Receptors, Androgen/*genetics ; Sequence Analysis ; Somatosensory Cortex/physiology ; Species Specificity ; Vibrissae/*metabolism/physiology ; }, abstract = {Previous studies show that humans have a large genomic deletion downstream of the Androgen Receptor gene that eliminates an ancestral mammalian regulatory enhancer that drives expression in developing penile spines and sensory vibrissae. Here we use a combination of large-scale sequence analysis and PCR amplification to demonstrate that the penile spine/vibrissa enhancer is missing in all humans surveyed and in the Neandertal and Denisovan genomes, but is present in DNA samples of chimpanzees and bonobos, as well as in multiple other great apes and primates that maintain some form of penile integumentary appendage and facial vibrissae. These results further strengthen the association between the presence of the penile spine/vibrissa enhancer and the presence of penile spines and macro- or micro- vibrissae in non-human primates as well as show that loss of the enhancer is both a distinctive and characteristic feature of the human lineage.}, }
@article {pmid24343584, year = {2014}, author = {Baklanova, YV and Denisova, TA and Maksimova, LG and Tyutyunnik, AP and Baklanova, IV and Shein, IR and Neder, RB and Tarakina, NV}, title = {Synthesis and characterisation of new MO(OH)2 (M = Zr, Hf) oxyhydroxides and related Li2MO3 salts.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {43}, number = {7}, pages = {2755-2763}, doi = {10.1039/c3dt52929k}, pmid = {24343584}, issn = {1477-9234}, abstract = {Two new solid MO(OH)2 (M = Zr, Hf) oxyhydroxides have been synthesised by an ion-exchange reaction from Li2MO3 (M = Zr, Hf) precursors obtained by a citrate combustion technique. The crystal structure of the oxyhydroxides has been solved by direct methods and refined using Rietveld full profile fitting based on X-ray powder diffraction data. Both oxyhydroxides crystallize in a P2(1)/c monoclinic unit cell and have a structure resembling that of the related salts. Detailed characterisation of the fine-structure features and chemical bonding in precursors and oxyhydroxide powders has been performed using vibrational spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, pair distribution function analysis and quantum-chemical modelling.}, }
@article {pmid24336922, year = {2014}, author = {Ding, Q and Hu, Y and Xu, S and Wang, J and Jin, L}, title = {Neanderthal introgression at chromosome 3p21.31 was under positive natural selection in East Asians.}, journal = {Molecular biology and evolution}, volume = {31}, number = {3}, pages = {683-695}, doi = {10.1093/molbev/mst260}, pmid = {24336922}, issn = {1537-1719}, mesh = {Adaptation, Physiological/genetics ; Alleles ; Animals ; Asian Continental Ancestry Group/*genetics ; Chromosomes, Human, Pair 3/*genetics ; Far East ; Genetic Variation ; Geography ; Haplotypes/genetics ; Humans ; Linkage Disequilibrium/genetics ; Models, Genetic ; Neanderthals/*genetics ; Pan troglodytes/genetics ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Recombination, Genetic/genetics ; *Selection, Genetic ; Time Factors ; }, abstract = {Studies of the Neanderthal and Denisovan genomes demonstrate archaic hominin introgression in Eurasians. Here, we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans. We also detected a signal of strong positive selection in this region only in East Asians. Our data indicate that likely candidate targets of selection include rs12488302-T and its associated alleles--among which four are nonsynonymous, including rs35455589-G in HYAL2, a gene related to the cellular response to ultraviolet-B irradiation. Furthermore, suggestive evidence supports latitude-dependent selection, implicating a role of ultraviolet-B. Interestingly, the distribution of rs35455589-G suggests that this allele was lost during the exodus of ancestors of modern Eurasians from Africa and reintroduced to Eurasians from Neanderthals.}, }
@article {pmid24262833, year = {2013}, author = {Marchi, E and Kanapin, A and Byott, M and Magiorkinis, G and Belshaw, R}, title = {Neanderthal and Denisovan retroviruses in modern humans.}, journal = {Current biology : CB}, volume = {23}, number = {22}, pages = {R994-R995}, doi = {10.1016/j.cub.2013.10.028}, pmid = {24262833}, issn = {1879-0445}, support = {MR/K010565/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Humans ; Neanderthals/*genetics ; Retroviridae/*genetics ; }, }
@article {pmid24244704, year = {2013}, author = {Derenko, M and Malyarchuk, B and Bahmanimehr, A and Denisova, G and Perkova, M and Farjadian, S and Yepiskoposyan, L}, title = {Complete mitochondrial DNA diversity in Iranians.}, journal = {PloS one}, volume = {8}, number = {11}, pages = {e80673}, doi = {10.1371/journal.pone.0080673}, pmid = {24244704}, issn = {1932-6203}, mesh = {DNA, Mitochondrial/*genetics ; European Continental Ancestry Group ; Gene Flow/genetics ; Genetics, Population ; Haplotypes ; Humans ; Iran ; Phylogeny ; }, abstract = {Due to its pivotal geographical location and proximity to transcontinental migratory routes, Iran has played a key role in subsequent migrations, both prehistoric and historic, between Africa, Asia and Europe. To shed light on the genetic structure of the Iranian population as well as on the expansion patterns and population movements which affected this region, the complete mitochondrial genomes of 352 Iranians were obtained. All Iranian populations studied here exhibit similarly high diversity values comparable to the other groups from the Caucasus, Anatolia and Europe. The results of AMOVA and MDS analyses did not associate any regional and/or linguistic group of populations in the Anatolia/Caucasus and Iran region pointing to close genetic positions of Persians and Qashqais to each other and to Armenians, and Azeris from Iran to Georgians. By reconstructing the complete mtDNA phylogeny of haplogroups R2, N3, U1, U3, U5a1g, U7, H13, HV2, HV12, M5a and C5c we have found a previously unexplored genetic connection between the studied Iranian populations and the Arabian Peninsula, India, Near East and Europe, likely the result of both ancient and recent gene flow. Our results for Persians and Qashqais point to a continuous increase of the population sizes from ∼24 kya to the present, although the phase between 14-24 kya is thought to be hyperarid according to the Gulf Oasis model. Since this would have affected hunter-gatherer ranges and mobility patterns and forced them to increasingly rely on coastal resources, this transition can explain the human expansion across the Persian Gulf region.}, }
@article {pmid24174545, year = {2013}, author = {Hochreiter, S}, title = {HapFABIA: identification of very short segments of identity by descent characterized by rare variants in large sequencing data.}, journal = {Nucleic acids research}, volume = {41}, number = {22}, pages = {e202}, doi = {10.1093/nar/gkt1013}, pmid = {24174545}, issn = {1362-4962}, mesh = {*Genetic Variation ; Genomics ; Genotyping Techniques ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Inheritance Patterns ; Sequence Analysis, DNA/*methods ; }, abstract = {Identity by descent (IBD) can be reliably detected for long shared DNA segments, which are found in related individuals. However, many studies contain cohorts of unrelated individuals that share only short IBD segments. New sequencing technologies facilitate identification of short IBD segments through rare variants, which convey more information on IBD than common variants. Current IBD detection methods, however, are not designed to use rare variants for the detection of short IBD segments. Short IBD segments reveal genetic structures at high resolution. Therefore, they can help to improve imputation and phasing, to increase genotyping accuracy for low-coverage sequencing and to increase the power of association studies. Since short IBD segments are further assumed to be old, they can shed light on the evolutionary history of humans. We propose HapFABIA, a computational method that applies biclustering to identify very short IBD segments characterized by rare variants. HapFABIA is designed to detect short IBD segments in genotype data that were obtained from next-generation sequencing, but can also be applied to DNA microarray data. Especially in next-generation sequencing data, HapFABIA exploits rare variants for IBD detection. HapFABIA significantly outperformed competing algorithms at detecting short IBD segments on artificial and simulated data with rare variants. HapFABIA identified 160 588 different short IBD segments characterized by rare variants with a median length of 23 kb (mean 24 kb) in data for chromosome 1 of the 1000 Genomes Project. These short IBD segments contain 752 000 single nucleotide variants (SNVs), which account for 39% of the rare variants and 23.5% of all variants. The vast majority-152 000 IBD segments-are shared by Africans, while only 19 000 and 11 000 are shared by Europeans and Asians, respectively. IBD segments that match the Denisova or the Neandertal genome are found significantly more often in Asians and Europeans but also, in some cases exclusively, in Africans. The lengths of IBD segments and their sharing between continental populations indicate that many short IBD segments from chromosome 1 existed before humans migrated out of Africa. Thus, rare variants that tag these short IBD segments predate human migration from Africa. The software package HapFABIA is available from Bioconductor. All data sets, result files and programs for data simulation, preprocessing and evaluation are supplied at http://www.bioinf.jku.at/research/short-IBD.}, }
@article {pmid24132124, year = {2013}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Khoyt, S and Woźniak, M and Grzybowski, T and Zakharov, I}, title = {Y-chromosome diversity in the Kalmyks at the ethnical and tribal levels.}, journal = {Journal of human genetics}, volume = {58}, number = {12}, pages = {804-811}, doi = {10.1038/jhg.2013.108}, pmid = {24132124}, issn = {1435-232X}, mesh = {Asian Continental Ancestry Group/*genetics ; Chromosomes, Human, Y/*genetics ; Ethnic Groups/*genetics ; European Continental Ancestry Group/*genetics ; Gene Flow/genetics ; Gene Frequency/genetics ; Genetics, Population ; Haplotypes ; Humans ; Male ; Microsatellite Repeats/genetics ; Polymorphism, Genetic/*genetics ; }, abstract = {The Mongolic-speaking Kalmyks currently inhabiting the steppes of the Volga region have Central Asian ancestry and are organized into the tribal groups. The genetic relationships among these tribes and their origin have remained obscure. We analyzed 17 short tandem repeat and 44 binary polymorphisms of Y-chromosome in 426 individuals mainly from three major tribes of the Kalmyks (the Torguuds, Dörwöds and Khoshuuds). Among these tribes, the Dörwöds and Torguuds, as well as the Kalmyks collectively as an ethnic group, showed relatively close genetic affinities to each other and to the Mongols and Altaian Kazakhs, whereas the Khoshuuds were clearly separated from all of them, gathering with the Manchu, Tibetans or Evenks (depending on the algorithm used to calculate genetic distances). The genetic results also indicate that paternal gene flow from East Europeans to the Kalmyks is very little, despite their cohabitation in the North Caspian Steppe during the last 380 years. The occurrence of unique cluster of N1c-Tat haplotypes in the Khoshuuds, which dates to about 340 years and is likely to have East European ancestry, is considered as a result of interethnic contacts occurred soon after the appearance of the Kalmyk tribes in the Volga-Ural region.}, }
@article {pmid24064255, year = {2014}, author = {Malyarchuk, B and Derenko, M and Mikhailova, E and Denisova, G}, title = {Phylogenetic relationships among Neoechinorhynchus species (Acanthocephala: Neoechinorhynchidae) from North-East Asia based on molecular data.}, journal = {Parasitology international}, volume = {63}, number = {1}, pages = {100-107}, doi = {10.1016/j.parint.2013.09.012}, pmid = {24064255}, issn = {1873-0329}, mesh = {Acanthocephala/*genetics ; Animals ; Asia/epidemiology ; DNA/genetics ; Demography ; Fish Diseases/epidemiology/parasitology ; Fishes ; *Genetic Variation ; Helminthiasis, Animal/epidemiology/parasitology ; *Phylogeny ; Species Specificity ; }, abstract = {Phylogenetic and statistical analyses of DNA sequences of two genes, cytochrome oxidase subunit 1 (cox 1) of the mitochondrial DNA and 18S subunit of the nuclear ribosomal RNA (18S rRNA), was used to characterize Neoechinorhynchus species from fishes collected in different localities of North-East Asia. It has been found that four species can be clearly recognized using molecular markers-Neoechinorhynchus tumidus, Neoechinorhynchus beringianus, Neoechinorhynchus simansularis and Neoechinorhynchus salmonis. 18S sequences ascribed to Neoechinorhynchus crassus specimens from North-East Asia were identical to those of N. tumidus, but differed substantially from North American N. crassus. We renamed North-East Asian N. crassus specimens to N. sp., although the possibility that they represent a subspecies of N. tumidus cannot be excluded, taking into account a relatively small distance between cox 1 sequences of North-East Asian specimens of N. crassus and N. tumidus. Maximum likelihood, maximum parsimony and Bayesian inference analyses were performed for phylogeny reconstruction. All the phylogenetic trees showed that North-East Asian species of Neoechinorhynchus analyzed in this study represent independent clades, with the only exception of N. tumidus and N. sp. for 18S data. Phylogenetic analysis has shown that the majority of species sampled (N. tumidus+N. sp., N. simansularis and N. beringianus) are probably very closely related, while N. salmonis occupies separate position in the trees, possibly indicating a North American origin of this species.}, }
@article {pmid23980394, year = {2013}, author = {Ovchinnikov, IV}, title = {Hominin evolution and gene flow in the Pleistocene Africa.}, journal = {Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur}, volume = {70}, number = {2}, pages = {221-227}, pmid = {23980394}, issn = {0003-5548}, mesh = {Africa ; Animals ; Anthropology, Physical ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Fossils ; *Gene Flow ; Genome, Mitochondrial/genetics ; Hominidae/*genetics ; Humans ; Phylogeny ; }, abstract = {Africa demonstrates a complex process of the hominin evolution with a series of adaptive radiations during several millions of years that led to diverse morphological forms. Recently, Hammer et al. (2011) and Harvati et al. (2011) provided integrated morphological and genetic evidence of interbreeding between modern humans and unknown archaic hominins in Africa as recently as 35,000 years ago. However, a genetic evidence of hybridization between hominin lineages during the Lower and Middle Pleistocene epochs is unknown and the direct retrieval of DNA from extinct lineages of African hominins remains elusive. The availability of both nuclear and mitochondrial genome sequences from modern humans, Neanderthals, and Denisovans allows collecting nuclear DNA sequences of mitochondrial origin (numts) inserted into the nuclear genome of the ancestral hominin lineages and drawing conclusions about the hominin evolution in the remote past. The mtDNA and numt analysis uncovered a deep division of mtDNA lineages that existed in African hominins in the Middle Pleistocene. The first cluster included the human and Neanderthal-like mtDNA sequences while the second consisted of DNA sequences that are known today as mtAncestor-1, a nuclear fossil of the mtDNA, and the Denisova mtDNA isolated from a bone and a tooth found in southern Siberia. The two groups initially diverged 610,000-1,110,000 years ago. Approximately 220,000 years after the primary split, the Denisova - mtAncestor-1 mtDNA lineages mixed with the mtDNA pool of an ancestral population of Neanderthals and modern humans. This admixture after the profound division is demonstrated by the transposition of the Denisova-like mtDNA sequence into the nuclear genome of an ancestor of Neanderthals and modern humans. This finding suggests the matrilineal genetic structure among the Middle Pleistocene hominins as well as the existence of gene flow between African hominin lineages. Through paleogenomic analyses, it is impossible to exclude the theory that population structure and gene flow in African hominins influenced the admixture pattern observed in the nuclear genomes of non-Africans.}, }
@article {pmid23959642, year = {2012}, author = {Setó-Salvia, N and Sánchez-Quinto, F and Carbonell, E and Lorenzo, C and Comas, D and Clarimón, J}, title = {Using the neanderthal and denisova genetic data to understand the common MAPT 17q21 inversion in modern humans.}, journal = {Human biology}, volume = {84}, number = {6}, pages = {633-640}, doi = {10.3378/027.084.0605}, pmid = {23959642}, issn = {1534-6617}, mesh = {Alleles ; Animals ; Biological Evolution ; *Chromosome Inversion ; Genome, Human ; Haplotypes ; Hominidae/*genetics ; Humans ; Linkage Disequilibrium ; Neanderthals/genetics ; Polymorphism, Genetic ; tau Proteins/*genetics ; }, abstract = {The polymorphic inversion on 17q21, that includes the MAPT gene, represents a unique locus in the human genome characterized by a large region with strong linkage disequilibrium. Two distinct haplotypes, H1 and H2, exist in modern humans, and H1 has been unequivocally related to several neurodegenerative disorders. Recent data indicate that recurrent inversions of this genomic region have occurred through primate evolution, with the H2 haplotype being the ancestral state. Neandertals harbored the H1 haplotype; however, until now, no data were available for the Denisova hominin. Neandertals and Denisovans are sister groups that share a common ancestor with modern humans. We analyzed the MAPT sequence and assessed the differences between modern humans, Neandertals, Denisovans, and great apes. Our analysis indicated that the Denisova hominin carried the H1 haplotype, and the Neandertal and Denisova common ancestor probably shared the same subhaplotype (H1j). We also found 68 intronic variants within the MAPT gene, 23 exclusive to Denisova hominin, 6 limited to Neandertals, and 24 exclusive to present-day humans. Our results reinforce previous data; this suggests that the 17q21 inversion arose within the modern human lineage. The data also indicate that archaic hominins that coexisted in Eurasia probably shared the same MAPT subhaplotype, and this can be found in almost 2% of chromosomes from European ancestry.}, }
@article {pmid23951901, year = {2013}, author = {Agafonova, EV and Malanicheva, TG and Denisova, SN}, title = {[Defects of neutrophil function in chronic gastroduodenitis in children].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {1}, pages = {60-63}, pmid = {23951901}, issn = {1682-8658}, mesh = {Adolescent ; Candida albicans/isolation & purification ; Candidiasis/*blood/complications/microbiology/pathology ; Case-Control Studies ; Child ; Chronic Disease ; Data Interpretation, Statistical ; Duodenitis/*blood/complications/microbiology/pathology ; Gastritis/*blood/complications/microbiology/pathology ; Helicobacter Infections/*blood/complications/microbiology/pathology ; Helicobacter pylori/isolation & purification ; Humans ; Neutrophils/immunology/*physiology ; Phagocytosis/physiology ; }, abstract = {At present, chronic gastroduodenitis (CGD) occupies one ofthe leading places in the structure of diseases of the gastrointestinal tract in children. In the etiology of CGD, along with the leading pathogenic Helicobacterpylori (HP), the role of the fungal flora increased. The aim of the work was to evaluate the functional activity of neutrophils in children with the CGD, associated with HP and Candida albicans. Among 110 children in the age from 7 to 17 years with chronic gastroduodenitis, associated with Helicobacter pylory(HP), as well as the association of HP with Candida albicans and the markers of secondary immune insufficiency, a study of the phagocytic activity and immune phenotype of neutrophils by flow cytofluorimetry was conducted. Differentiated peculiarities of the phagocytic activity of neutrophils in association with bacterial pathogens (HP) and fungal flora were identified. The transformation of the immune phenotype was combined with a significant depression of the phagocytic and microbicidal functions, more pronounced with the association of HP and Candida albicans. Circulating mannano protein antigen of Candida albicans influenced on the surface of phenotype of neutrophils, increasing the expression of protopathic and HLADR-receptors, and decreasing the expression of adhesion receptors and cytolysis. Thus, in case of chronic gastroduodenitis in children, there was a considerable transformation of the phenotype of neutrophil with differentiated characteristics at the association with bacterial (HP) pathogens and fungal flora. The obtained data should be taken into account when carrying out medical activities, and the doctors should include in the composition of complex therapy of CGD, associated with Candida albicans, drugs, aimed at immunocorrection of the identified violations}, }
@article {pmid23906376, year = {2013}, author = {Hedrick, PW}, title = {Adaptive introgression in animals: examples and comparison to new mutation and standing variation as sources of adaptive variation.}, journal = {Molecular ecology}, volume = {22}, number = {18}, pages = {4606-4618}, doi = {10.1111/mec.12415}, pmid = {23906376}, issn = {1365-294X}, mesh = {Adaptation, Biological/*genetics ; Animals ; *Evolution, Molecular ; Genetic Variation ; Humans ; Models, Genetic ; Mutation ; *Selection, Genetic ; }, abstract = {Adaptive genetic variation has been thought to originate primarily from either new mutation or standing variation. Another potential source of adaptive variation is adaptive variants from other (donor) species that are introgressed into the (recipient) species, termed adaptive introgression. Here, the various attributes of these three potential sources of adaptive variation are compared. For example, the rate of adaptive change is generally thought to be faster from standing variation, slower from mutation and potentially intermediate from adaptive introgression. Additionally, the higher initial frequency of adaptive variation from standing variation and lower initial frequency from mutation might result in a higher probability of fixation of the adaptive variants for standing variation. Adaptive variation from introgression might have higher initial frequency than new adaptive mutations but lower than that from standing variation, again making the impact of adaptive introgression variation potentially intermediate. Adaptive introgressive variants might have multiple changes within a gene and affect multiple loci, an advantage also potentially found for adaptive standing variation but not for new adaptive mutants. The processes that might produce a common variant in two taxa, convergence, trans-species polymorphism from incomplete lineage sorting or from balancing selection and adaptive introgression, are also compared. Finally, potential examples of adaptive introgression in animals, including balancing selection for multiple alleles for major histocompatibility complex (MHC), S and csd genes, pesticide resistance in mice, black colour in wolves and white colour in coyotes, Neanderthal or Denisovan ancestry in humans, mimicry genes in Heliconius butterflies, beak traits in Darwin's finches, yellow skin in chickens and non-native ancestry in an endangered native salamander, are examined.}, }
@article {pmid23889734, year = {2013}, author = {Bimbo, LM and Denisova, OV and Mäkilä, E and Kaasalainen, M and De Brabander, JK and Hirvonen, J and Salonen, J and Kakkola, L and Kainov, D and Santos, HA}, title = {Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles.}, journal = {ACS nano}, volume = {7}, number = {8}, pages = {6884-6893}, doi = {10.1021/nn402062f}, pmid = {23889734}, issn = {1936-086X}, support = {310892//European Research Council/International ; }, mesh = {Amides/*administration & dosage ; Animals ; Dogs ; Drug Carriers ; Drug Delivery Systems ; Humans ; Influenza A virus/*drug effects ; Influenza, Human/*drug therapy ; Madin Darby Canine Kidney Cells ; Microscopy, Fluorescence ; Models, Chemical ; Nanoparticles/*chemistry ; Nanotechnology/*methods ; Particle Size ; Salicylates/*administration & dosage ; Silicon/*chemistry ; Solvents/chemistry ; }, abstract = {Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells.}, }
@article {pmid23887633, year = {2013}, author = {Kakkola, L and Denisova, OV and Tynell, J and Viiliäinen, J and Ysenbaert, T and Matos, RC and Nagaraj, A and Ohman, T and Kuivanen, S and Paavilainen, H and Feng, L and Yadav, B and Julkunen, I and Vapalahti, O and Hukkanen, V and Stenman, J and Aittokallio, T and Verschuren, EW and Ojala, PM and Nyman, T and Saelens, X and Dzeyk, K and Kainov, DE}, title = {Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice.}, journal = {Cell death & disease}, volume = {4}, number = {}, pages = {e742}, doi = {10.1038/cddis.2013.267}, pmid = {23887633}, issn = {2041-4889}, mesh = {Aniline Compounds/*pharmacology ; Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cytokines/biosynthesis ; Disease Models, Animal ; Influenza A virus/physiology ; Macrophages/metabolism ; Mice ; Neoplasms/*drug therapy/pathology/virology ; Orthomyxoviridae Infections/metabolism/pathology ; Sulfonamides/*pharmacology ; }, abstract = {ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections.}, }
@article {pmid23872234, year = {2013}, author = {Lowery, RK and Uribe, G and Jimenez, EB and Weiss, MA and Herrera, KJ and Regueiro, M and Herrera, RJ}, title = {Neanderthal and Denisova genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.}, journal = {Gene}, volume = {530}, number = {1}, pages = {83-94}, doi = {10.1016/j.gene.2013.06.005}, pmid = {23872234}, issn = {1879-0038}, mesh = {Africa South of the Sahara ; Animals ; DNA, Mitochondrial/genetics ; Europe ; Fossils ; Genetic Drift ; Genetics, Population ; Genome, Human ; Humans ; Neanderthals/*genetics ; Pan troglodytes/genetics ; *Phylogeny ; *Polymorphism, Genetic ; }, abstract = {Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations.}, }
@article {pmid23755774, year = {2013}, author = {Mandras, N and Roana, J and Allizond, V and Pasqualini, D and Crosasso, P and Burlando, M and Banche, G and Denisova, T and Berutti, E and Cuffini, AM}, title = {Antibacterial efficacy and drug-induced tooth discolouration of antibiotic combinations for endodontic regenerative procedures.}, journal = {International journal of immunopathology and pharmacology}, volume = {26}, number = {2}, pages = {557-563}, doi = {10.1177/039463201302600232}, pmid = {23755774}, issn = {0394-6320}, mesh = {Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/*adverse effects ; Ciprofloxacin/adverse effects ; Clarithromycin/adverse effects ; Dental Pulp Cavity/microbiology/*surgery ; Drug Therapy, Combination ; Female ; Fosfomycin/adverse effects ; Humans ; Male ; Metronidazole/adverse effects ; Middle Aged ; Minocycline/adverse effects ; Root Canal Irrigants/*adverse effects ; Root Canal Preparation/*adverse effects ; Therapeutic Irrigation/*adverse effects ; Tooth Discoloration/chemically induced/*prevention & control ; Tooth, Nonvital/microbiology/*surgery ; Young Adult ; }, abstract = {Elimination of microbial contamination from the root canal system is a precondition for successful root canal treatment. Teeth with immature root development, necrotic pulps and apical periodontitis present multiple challenges for successful treatment. Disinfection is achieved by irrigation followed by the placement of an intracanal medicament. A mixture of ciprofloxacin, metronidazole and minocycline (3-MIX S) has been shown to be very effective in eliminating endodontic pathogens in vitro and in vivo. Among the components of the mixture, minocycline can induce tooth discolouration after long-term oral use. Therefore, the elimination of minocycline from the above-mentioned combination has been suggested to prevent the occasion of this undesirable effect. The aim of this study was to investigate the potential antimicrobial efficacy of alternative antibiotic combinations [3-MIX C (clarithromycin); 3-MIX F (fosfomycin)] against bacteria from infected root canals. An additional objective was to evaluate their discolouration potential as possible alternatives to minocycline-based intracanal medicaments. Our in vitro results clearly demonstrated that 3-MIX C and 3-MIX F had a greater antimicrobial activity than 3-MIX S, underlying that clarithromycin still had a higher capacity to kill endodontic pathogens in vitro compared to fosfomycin. Both 3-MIX C and 3-MIX F were able to avoid the permanent staining effect of the crown.}, }
@article {pmid23687020, year = {2013}, author = {Pennisi, E}, title = {Human evolution. More genomes from Denisova Cave show mixing of early human groups.}, journal = {Science (New York, N.Y.)}, volume = {340}, number = {6134}, pages = {799}, doi = {10.1126/science.340.6134.799}, pmid = {23687020}, issn = {1095-9203}, mesh = {Animals ; Anthropology ; *Biological Evolution ; *Caves ; DNA/genetics ; *Genome, Human ; Humans ; Neanderthals/*genetics ; Sequence Analysis, DNA/*methods ; Siberia ; Toe Phalanges ; }, }
@article {pmid23677594, year = {2013}, author = {Dormitzer, PR and Suphaphiphat, P and Gibson, DG and Wentworth, DE and Stockwell, TB and Algire, MA and Alperovich, N and Barro, M and Brown, DM and Craig, S and Dattilo, BM and Denisova, EA and De Souza, I and Eickmann, M and Dugan, VG and Ferrari, A and Gomila, RC and Han, L and Judge, C and Mane, S and Matrosovich, M and Merryman, C and Palladino, G and Palmer, GA and Spencer, T and Strecker, T and Trusheim, H and Uhlendorff, J and Wen, Y and Yee, AC and Zaveri, J and Zhou, B and Becker, S and Donabedian, A and Mason, PW and Glass, JI and Rappuoli, R and Venter, JC}, title = {Synthetic generation of influenza vaccine viruses for rapid response to pandemics.}, journal = {Science translational medicine}, volume = {5}, number = {185}, pages = {185ra68}, doi = {10.1126/scitranslmed.3006368}, pmid = {23677594}, issn = {1946-6242}, support = {HHSN272200900007C//PHS HHS/United States ; HHSO100201000061C//PHS HHS/United States ; }, mesh = {Animals ; Cell Line ; Computer Simulation ; Dogs ; Genes, Synthetic ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Humans ; Influenza A Virus, H7N9 Subtype/immunology ; Influenza A virus/*immunology ; Influenza Vaccines/*immunology ; Influenza, Human/*immunology/*prevention & control/virology ; Madin Darby Canine Kidney Cells ; Neuraminidase/genetics ; Pandemics/*prevention & control ; Reassortant Viruses/immunology ; Reproducibility of Results ; Vaccines, Synthetic/*immunology ; Viral Load ; }, abstract = {During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.}, }
@article {pmid23666864, year = {2013}, author = {Elhaik, E and Greenspan, E and Staats, S and Krahn, T and Tyler-Smith, C and Xue, Y and Tofanelli, S and Francalacci, P and Cucca, F and Pagani, L and Jin, L and Li, H and Schurr, TG and Greenspan, B and Spencer Wells, R and , }, title = {The GenoChip: a new tool for genetic anthropology.}, journal = {Genome biology and evolution}, volume = {5}, number = {5}, pages = {1021-1031}, doi = {10.1093/gbe/evt066}, pmid = {23666864}, issn = {1759-6653}, support = {T32 MH014592/MH/NIMH NIH HHS/United States ; 098051//Wellcome Trust/United Kingdom ; }, mesh = {*Anthropology, Cultural ; DNA, Mitochondrial/*genetics ; Genes, Y-Linked ; History, Ancient ; Human Genome Project ; Human Migration/history ; Humans ; *Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/*genetics ; }, abstract = {The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project's new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. The GenoChip includes ancestry informative markers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all known Y-chromosome and mtDNA haplogroups. The chip was carefully vetted to avoid inclusion of medically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs without any known health, medical, or phenotypic relevance, the GenoChip is a useful tool for genetic anthropology and population genetics.}, }
@article {pmid23662523, year = {2012}, author = {Zabolotskikh, IB and Musaeva, TS and Denisova, EA}, title = {[Validity of APACHE II, APACHE III, SAPS 2, SAPS 3 and SOFA scales in obstetric patients with sepsis].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {6}, pages = {55-57}, pmid = {23662523}, issn = {0201-7563}, mesh = {*APACHE ; Adult ; Female ; Hospital Records/statistics & numerical data ; Humans ; *Organ Dysfunction Scores ; Pregnancy ; Pregnancy Complications, Infectious/*diagnosis ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; Sepsis/*diagnosis ; *Severity of Illness Index ; Young Adult ; }, abstract = {RESEARCH OBJECTIVE: to estimate efficiency of APACHE II, APACHE III, SAPS II, SAPS III, SOFA scales for obstetric patients with heavy sepsis.

MATERIALS AND METHODS: 186 medical cards retrospective analysis of pregnant women with pulmonary sepsis, 40 women with urosepsis and puerperas with abdominal sepsis--66 was performed. Middle age of women was 26.7 (22.4-34.5).

CONCLUSION: Prognostic possibilities assessment of score scales showed that APACHE III, SAPS 3 and SOFA scales can be used for a lethality prognosis for puerperas with abdominal sepsis, in population of pregnant women with urosepsis--only APACHE III and SOFA, and with pulmonary sepsis--SAPS 3 and APACHE III only in case of additional clinical information.}, }
@article {pmid23657884, year = {2013}, author = {Contreras-Galindo, R and Kaplan, MH and He, S and Contreras-Galindo, AC and Gonzalez-Hernandez, MJ and Kappes, F and Dube, D and Chan, SM and Robinson, D and Meng, F and Dai, M and Gitlin, SD and Chinnaiyan, AM and Omenn, GS and Markovitz, DM}, title = {HIV infection reveals widespread expansion of novel centromeric human endogenous retroviruses.}, journal = {Genome research}, volume = {23}, number = {9}, pages = {1505-1513}, doi = {10.1101/gr.144303.112}, pmid = {23657884}, issn = {1549-5469}, support = {R01 AI062248/AI/NIAID NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; 1F31CA150523-01/CA/NCI NIH HHS/United States ; 5T32AI007528-13/AI/NIAID NIH HHS/United States ; UL1RR24986/RR/NCRR NIH HHS/United States ; U54DA021519/DA/NIDA NIH HHS/United States ; F31 CA150523/CA/NCI NIH HHS/United States ; 3R01CA144043-03S1/CA/NCI NIH HHS/United States ; R01AI062248/AI/NIAID NIH HHS/United States ; P30 ES017885/ES/NIEHS NIH HHS/United States ; U54 DA021519/DA/NIDA NIH HHS/United States ; UL1 RR024986/RR/NCRR NIH HHS/United States ; P30U54ES017885/ES/NIEHS NIH HHS/United States ; R01 CA144043/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Centromere/genetics/virology ; Chromosomes, Human/genetics/virology ; Endogenous Retroviruses/*genetics ; Evolution, Molecular ; *Genome, Human ; HIV Infections/*genetics ; Hominidae/genetics/virology ; Humans ; Proviruses/*genetics ; *Virus Integration ; tat Gene Products, Human Immunodeficiency Virus/genetics/metabolism ; }, abstract = {Human endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV-K (HML-2) family is the most recent group of these viruses to have inserted into the genome, and we have detected the activation of HERV-K (HML-2) proviruses in the blood of patients with HIV-1 infection. We report that HIV-1 infection activates expression of a novel HERV-K (HML-2) provirus, termed K111, present in multiple copies in the centromeres of chromosomes throughout the human genome yet not annotated in the most recent human genome assembly. Infection with HIV-1 or stimulation with the HIV-1 Tat protein leads to the activation of K111 proviruses. K111 is present as a single copy in the genome of the chimpanzee, yet K111 is not found in the genomes of other primates. Remarkably, K111 proviruses appear in the genomes of the extinct Neanderthal and Denisovan, while modern humans have at least 100 K111 proviruses spread across the centromeres of 15 chromosomes. Our studies suggest that the progenitor K111 integrated before the Homo-Pan divergence and expanded in copy number during the evolution of hominins, perhaps by recombination. The expansion of K111 provides sequence evidence suggesting that recombination between the centromeres of various chromosomes took place during the evolution of humans. K111 proviruses show significant sequence variations in each individual centromere, which may serve as markers in future efforts to annotate human centromere sequences. Further, this work is an example of the potential to discover previously unknown genomic sequences through the analysis of nucleic acids found in the blood of patients.}, }
@article {pmid23553074, year = {2013}, author = {Khairat, R and Ball, M and Chang, CC and Bianucci, R and Nerlich, AG and Trautmann, M and Ismail, S and Shanab, GM and Karim, AM and Gad, YZ and Pusch, CM}, title = {First insights into the metagenome of Egyptian mummies using next-generation sequencing.}, journal = {Journal of applied genetics}, volume = {54}, number = {3}, pages = {309-325}, doi = {10.1007/s13353-013-0145-1}, pmid = {23553074}, issn = {2190-3883}, mesh = {Base Sequence ; Biopsy ; Egypt, Ancient ; Embalming/history/*methods ; Gene Library ; History, Ancient ; Humans ; *Metagenome ; Molecular Sequence Data ; *Mummies ; Phylogeny ; Plasmodium falciparum/genetics ; Polymerase Chain Reaction/methods ; Sequence Analysis, DNA/methods ; Temperature ; Toxoplasma/genetics ; }, abstract = {We applied, for the first time, next-generation sequencing (NGS) technology on Egyptian mummies. Seven NGS datasets obtained from five randomly selected Third Intermediate to Graeco-Roman Egyptian mummies (806 BC-124AD) and two unearthed pre-contact Bolivian lowland skeletons were generated and characterised. The datasets were contrasted to three recently published NGS datasets obtained from cold-climate regions, i.e. the Saqqaq, the Denisova hominid and the Alpine Iceman. Analysis was done using one million reads of each newly generated or published dataset. Blastn and megablast results were analysed using MEGAN software. Distinct NGS results were replicated by specific and sensitive polymerase chain reaction (PCR) protocols in ancient DNA dedicated laboratories. Here, we provide unambiguous identification of authentic DNA in Egyptian mummies. The NGS datasets showed variable contents of endogenous DNA harboured in tissues. Three of five mummies displayed a human DNA proportion comparable to the human read count of the Saqqaq permafrost-preserved specimen. Furthermore, a metagenomic signature unique to mummies was displayed. By applying a "bacterial fingerprint", discrimination among mummies and other remains from warm areas outside Egypt was possible. Due to the absence of an adequate environment monitoring, a bacterial bloom was identified when analysing different biopsies from the same mummies taken after a lapse of time of 1.5 years. Plant kingdom representation in all mummy datasets was unique and could be partially associated with their use in embalming materials. Finally, NGS data showed the presence of Plasmodium falciparum and Toxoplasma gondii DNA sequences, indicating malaria and toxoplasmosis in these mummies. We demonstrate that endogenous ancient DNA can be extracted from mummies and serve as a proper template for the NGS technique, thus, opening new pathways of investigation for future genome sequencing of ancient Egyptian individuals.}, }
@article {pmid23415986, year = {2013}, author = {Malyarchuk, B and Derenko, M and Denisova, G}, title = {Phylogeny and genetic history of the Siberian salamander (Salamandrella keyserlingii, Dybowski, 1870) inferred from complete mitochondrial genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {67}, number = {2}, pages = {348-357}, doi = {10.1016/j.ympev.2013.02.004}, pmid = {23415986}, issn = {1095-9513}, mesh = {Animals ; Genetics, Population ; *Genome, Mitochondrial ; Haplotypes ; *Phylogeny ; Russia ; Sequence Analysis, DNA ; Siberia ; *Urodela/classification/genetics ; }, abstract = {We assessed phylogeny of the Siberian salamander (Salamandrella keyserlingii, Dybowski, 1870), the most northern ectothermic, terrestrial vertebrate in Eurasia, by sequence analysis of complete mitochondrial genomes in 26 specimens from different localities (China, Khabarovsk region, Sakhalin, Yakutia, Magadan region, Chukotka, Kamchatka, Ural, European part of Russia). In addition, a complete mitochondrial genome of the Schrenck salamander, Salamandrella schrenckii, was determined for the first time. Bayesian phylogenetic analysis of the entire mtDNA genomes of S. keyserlingii demonstrates that two haplotype clades, AB and C, radiated about 1.4 million years ago (Mya). Bayesian skyline plots of population size change through time show an expansion around 250 thousand years ago (kya) and then a decline around the Last Glacial Maximum (25 kya) with subsequent restoration of population size. Climatic changes during the Quaternary period have dramatically affected the population genetic structure of the Siberian salamanders. In addition, complete mtDNA sequence analysis allowed us to recognize that the vast area of Northern Eurasia was colonized only by the Siberian salamander clade C1b during the last 150 kya. Meanwhile, we were unable to find evidence of molecular adaptation in this clade by analyzing the whole mitochondrial genomes of the Siberian salamanders.}, }
@article {pmid23413113, year = {2012}, author = {Paixão-Côrtes, VR and Viscardi, LH and Salzano, FM and Hünemeier, T and Bortolini, MC}, title = {Homo sapiens, Homo neanderthalensis and the Denisova specimen: New insights on their evolutionary histories using whole-genome comparisons.}, journal = {Genetics and molecular biology}, volume = {35}, number = {4 (suppl)}, pages = {904-911}, pmid = {23413113}, issn = {1415-4757}, abstract = {After a brief review of the most recent findings in the study of human evolution, an extensive comparison of the complete genomes of our nearest relative, the chimpanzee (Pan troglodytes), of extant Homo sapiens, archaic Homo neanderthalensis and the Denisova specimen were made. The focus was on non-synonymous mutations, which consequently had an impact on protein levels and these changes were classified according to degree of effect. A total of 10,447 non-synonymous substitutions were found in which the derived allele is fixed or nearly fixed in humans as compared to chimpanzee. Their most frequent location was on chromosome 21. Their presence was then searched in the two archaic genomes. Mutations in 381 genes would imply radical amino acid changes, with a fraction of these related to olfaction and other important physiological processes. Eight new alleles were identified in the Neanderthal and/or Denisova genetic pools. Four others, possibly affecting cognition, occured both in the sapiens and two other archaic genomes. The selective sweep that gave rise to Homo sapiens could, therefore, have initiated before the modern/archaic human divergence.}, }
@article {pmid23402178, year = {2012}, author = {Malanichevskaia, TG and Narykov, RKh and Denisova, SN}, title = {[Peculiarities of diet therapy in children with duodenal ulcers associated with the genus Candida].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {5}, pages = {87-90}, pmid = {23402178}, issn = {1682-8658}, mesh = {Adolescent ; Animals ; Biopsy ; *Candida ; Candidiasis/*diet therapy/microbiology/pathology ; Child ; Duodenal Ulcer/*diet therapy/microbiology/pathology ; Female ; Goats ; Humans ; Intestinal Mucosa/microbiology/pathology ; Male ; Milk ; }, abstract = {In children with relapsing DU in 50.8% cases there is a complicated disease course with Candida infection, as evidenced by the positive results of mycological examination of biopsy specimens of duodenal mucosa and detection of circulating Candida antigen in serum. The use in the complex therapy in children with DU associated with Candida species of instant New Zealand goat milk "Amalteya" leads to an overall therapeutic effect in 81.3% cases, which is manifested in the reduction of the duration of relapse 1.4 times prolongation of remission in 3 times and milder disease. Carried out in the dynamics fibrogastroduodenoscopy after treatment showed that 100% of the observed total endoscopic remission which is manifested in the disappearance of opalescent gray overlay on the bottom of the ulcer and ulcer epithelization.}, }
@article {pmid23315957, year = {2013}, author = {Mendez, FL and Watkins, JC and Hammer, MF}, title = {Neandertal origin of genetic variation at the cluster of OAS immunity genes.}, journal = {Molecular biology and evolution}, volume = {30}, number = {4}, pages = {798-801}, doi = {10.1093/molbev/mst004}, pmid = {23315957}, issn = {1537-1719}, mesh = {2',5'-Oligoadenylate Synthetase/*genetics ; Animals ; Evolution, Molecular ; Genetic Loci/*immunology ; Genetic Speciation ; Gorilla gorilla/genetics ; Haplotypes ; Humans ; Linkage Disequilibrium ; Models, Genetic ; Multigene Family ; Neanderthals/*genetics ; Pan troglodytes/genetics ; Phylogeography ; *Polymorphism, Single Nucleotide ; }, abstract = {Analyses of ancient DNA from extinct humans reveal signals of at least two independent hybridization events in the history of non-African populations. To date, there are very few examples of specific genetic variants that have been rigorously identified as introgressive. Here, we survey DNA sequence variation in the OAS gene cluster on chromosome 12 and provide strong evidence that a haplotype extending for ~185 kb introgressed from Neandertals. This haplotype is nearly restricted to Eurasians and is estimated to have diverged from the Neandertal sequence ~125 kya. Despite the potential for novel functional variation, the observed frequency of this haplotype is consistent with neutral introgression. This is the second locus in the human genome, after STAT2, carrying distinct haplotypes that appear to have introgressed separately from both Neandertals and Denisova.}, }
@article {pmid24933983, year = {2013}, author = {Reshetnikov, OV and Kurilovich, SA and Denisova, DV}, title = {[Symptoms of gastroesophageal reflux disease and associated factors in adolescents: population survey].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {12}, pages = {8-14}, pmid = {24933983}, issn = {1682-8658}, mesh = {Adolescent ; Antibodies, Bacterial/blood ; Female ; *Gastroesophageal Reflux/diagnosis/epidemiology/etiology ; Helicobacter Infections/complications/epidemiology/microbiology ; Helicobacter pylori/isolation & purification ; Humans ; Male ; *Population Surveillance ; Prevalence ; Risk Factors ; Sex Factors ; Siberia/epidemiology ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Gastroesophageal reflux (GER) is frequent among the general population affecting 10-20% of adults. However, there is a notable lack of epidemiological data describing prevalence of GER in children. The aims of the present study were to assess the prevalence of GER symptoms (GERS) in adolescents and to evaluate factors associated with GERS including markers of H. pylori infection.

METHODS: All school students in grades 9-11 in four randomly selected secondary schools in Novosibirsk participated (449 adolescents, 189 boys, 260 girls aged 14-17). They completed the Bowel Disease Questionnaire, life-style questionnaire, and sera were tested for antibodies against Helicobacter pylori infection.

RESULTS: Overall, 60% of adolescents experienced GERS (heartburn and/or acid regurgitation) over the previous year. GER symptoms on a monthly basis were reported by 22% of students, weekly GERS were reported by 9% of adolescents with the same frequency in both genders. GERS were related to family history of dyspepsia or GER, mother's lower educational attainment, overweight, unhealthy eating patterns, alcohol consumption, smoking, and H. pylori infection, as well as concomitant dyspepsia and irritable bowel syndrome. The majority of associations were more prominent in girls. Visiting a physician, endoscopic study, and school absenteeism were reported in the last year more frequently by adolescents with GERS vs those without GERS.

CONCLUSIONS: Gastroesophageal reflux symptoms are frequent among the adolescent population and result in frequent use of health care resources. Some precipitated factors found in this study are modifiable and may be corrected in adolescent population.}, }
@article {pmid24933954, year = {2013}, author = {Malanicheva, TG and Ziatdinova, NV and Denisova, SN}, title = {[Prevalence and risk factors of gastroduodenal and biliary system diseases in infants and preschool children].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {8}, pages = {77-80}, pmid = {24933954}, issn = {1682-8658}, mesh = {Age Factors ; Bile Duct Diseases/*epidemiology ; Child ; Child, Preschool ; Duodenal Diseases/*epidemiology ; Female ; Humans ; Infant ; Male ; Prevalence ; Risk Factors ; Stomach Diseases/*epidemiology ; }, abstract = {To study the prevalence and risk factors of digestive diseases in children performed continuous screening questionnaire 786 children from 1.5 to 7 years. Were Revealed that 47.1 +/- 3.5% of children have symptoms of diseases of the gastrointestinal tract and biliary system. This symptoms occur in children aged 4 to 7 years in 2.3 times more frequently than in children from 1.5 to 3 years. In-depth study was revealed that the frequency of biliary dyskinesia (BD) was 33 +/- 3.3%, chronic gastritis (CG) and gastroduodenitis (CGD)--6.2 +/- 1.8%, chronic cholecystitis--4.2 +/- 1.4%, functional disorders of the stomach (FSD)--2.8 +/- 1.2%, and peptic duodenal ulcer (DU)--0.3 + 0.4%. In the structure of digestive diseases in children from 1.5 to 7 years on the 1st place are BD--70% on the 2nd--CG and CGD--14.7% on the 3rd chronic cholecystitis--8.9%, on the 4th FSD-5.9% and 5th place DU-0.5%. For dispensary observation in the children's clinic with digestive diseases consist of only 7.9 +/- 1.9% of children, which is 5.9 times lower than according to the active diagnostics data. The leading medical and social risk factors and their complex influence on the formation of digestive disorders in infants and preschool children.}, }
@article {pmid24772875, year = {2013}, author = {Denisova, TL and Tiul'tiaeva, LA and Lipatova, TE and Bakulev, AL and Alipova, LN and Apanasevich, AV and Bezrodnaia, LA and Borisova, EA}, title = {[Tertiary syphilis of the pancreas and liver in 82-year-old patient: case study].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {7}, pages = {41-43}, pmid = {24772875}, issn = {1682-8658}, mesh = {Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage/therapeutic use ; Ceftriaxone/administration & dosage/therapeutic use ; Diagnosis, Differential ; *Diagnostic Errors ; Humans ; Liver Diseases/*diagnosis/drug therapy/pathology ; Liver Neoplasms/*diagnosis/secondary/surgery ; Male ; Pancreatic Diseases/*diagnosis/drug therapy/pathology ; Pancreatic Neoplasms/*diagnosis/pathology/surgery ; Syphilis/*diagnosis/drug therapy/pathology ; Syphilis Serodiagnosis ; Treatment Outcome ; }, abstract = {It has been described a clinical case of late diagnosis of syphilis of the pancreas and liver of elderly patients. Two years before that it was wrongly diagnosed with cancer of the pancreas with liver metastases, and the patient was operated on with the imposition of cholecystostomy. It was conducted appropriate therapy and reconstructive surgery after verification of the diagnosis of syphilis of the pancreas and liver.}, }
@article {pmid24640735, year = {2013}, author = {Alekseeva, EI and Baranov, AA and Mitenko, EV and Bzarova, TM and Valieva, SI and Denisova, RV and Isaeva, KB and Chistiakova, EG and Sleptsova, TV and Taĭbulatov, NI and Zelikovich, EI and Kurilenkov, GV}, title = {[Efficiency and safety of human monoclonal antibodies to TNF-alpha in children with juvenile idiopathic arthritis in primary and secondary ineffectiveness of other biologicals].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {11}, pages = {73-82}, pmid = {24640735}, issn = {0869-6047}, mesh = {Adalimumab ; Adolescent ; Antibodies, Monoclonal, Humanized/*immunology/therapeutic use ; Antirheumatic Agents/therapeutic use ; Arthritis, Juvenile/*drug therapy ; Biological Factors/*therapeutic use ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Male ; Retrospective Studies ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors/immunology ; }, abstract = {PURPOSE: To evaluate the safety and efficiency of adalimumab in children with severe refractory JIA with primary inefficiency, partial effect or loss of the effectiveness of other biologicals.

PATIENTS AND METHODS: The article presents the results of the retrospective observational study of the efficacy and safety of adalimumab in 68 patients aged 10 (3, 17) years with various embodiments of JIA, with the primary inefficiency or partial or loss of the effectiveness of other biologicals. JIA diagnosis established on the basis of criteria ILAR (International League of Associations for Rheumatology).

RESULTS: Efficacy was assessed during 1 year in 68 and 2 years--in 56 patients . At the 24th week we observed the improvement by criteria AKR 30, 50.70 in 100, 91 and 74% of patients, respectively, and at the 52th week--in 100, 96 and 90%, respectively. Inactive disease status was recorded in 55.8, 66.1 and 98.2% of study participants after 6 months, 1 and 2 years, respectively. Remission was achieved in 55.8 and 96.4% of patients after 1 and 2 years of observation, respectively.

To examine potential intraspecific variation, we sequenced the APOE gene of 32 chimpanzees. This sample included 20 captive individuals representing the western subspecies (P. troglodytes verus) and 12 wild individuals representing the eastern subspecies (P. t. schweinfurthii). Variation in our resulting sequences was limited to one non-coding, intronic SNP, which showed fixed differences between the two subspecies. We also compared APOE sequences for all available ape genera and fossil hominins. The bonobo APOE protein is identical to that of the chimpanzee, and the Denisovan APOE exhibits all four human-specific, non-synonymous changes and appears functionally similar to the human E4 allele.

CONCLUSIONS: We found no coding variation within and between chimpanzee populations, suggesting that the maintenance of functionally diverse APOE polymorphisms is a unique feature of human evolution.}, }
@article {pmid22946817, year = {2012}, author = {Bokma, F and van den Brink, V and Stadler, T}, title = {Unexpectedly many extinct hominins.}, journal = {Evolution; international journal of organic evolution}, volume = {66}, number = {9}, pages = {2969-2974}, doi = {10.1111/j.1558-5646.2012.01660.x}, pmid = {22946817}, issn = {1558-5646}, mesh = {Animals ; *Extinction, Biological ; *Genetic Speciation ; Hominidae/*genetics ; Humans ; Models, Genetic ; }, abstract = {Recent studies indicate that Neanderthal and Denisova hominins may have been separate species, while debate continues on the status of Homo floresiensis. The decade-long debate between "splitters," who recognize over 20 hominin species, and "lumpers," who maintain that all these fossils belong to just a few lineages, illustrates that we do not know how many extinct hominin species to expect. Here, we present probability distributions for the number of speciation events and the number of contemporary species along a branch of a phylogeny. With estimates of hominin speciation and extincton rates, we then show that the expected total number of extinct hominin species is 8, but may be as high as 27. We also show that it is highly unlikely that three very recent species disappeared due to natural, background extinction. This may indicate that human-like remains are too easily considered distinct species. Otherwise, the evidence suggesting that Neanderthal and the Denisova hominin represent distinct species implies a recent wave of extinctions, ostensibly driven by the only survivor, H. sapiens.}, }
@article {pmid22936568, year = {2012}, author = {Meyer, M and Kircher, M and Gansauge, MT and Li, H and Racimo, F and Mallick, S and Schraiber, JG and Jay, F and Prüfer, K and de Filippo, C and Sudmant, PH and Alkan, C and Fu, Q and Do, R and Rohland, N and Tandon, A and Siebauer, M and Green, RE and Bryc, K and Briggs, AW and Stenzel, U and Dabney, J and Shendure, J and Kitzman, J and Hammer, MF and Shunkov, MV and Derevianko, AP and Patterson, N and Andrés, AM and Eichler, EE and Slatkin, M and Reich, D and Kelso, J and Pääbo, S}, title = {A high-coverage genome sequence from an archaic Denisovan individual.}, journal = {Science (New York, N.Y.)}, volume = {338}, number = {6104}, pages = {222-226}, doi = {10.1126/science.1224344}, pmid = {22936568}, issn = {1095-9203}, support = {R01-GM40282/GM/NIGMS NIH HHS/United States ; R01 GM100233/GM/NIGMS NIH HHS/United States ; R01 GM040282/GM/NIGMS NIH HHS/United States ; GM100233/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; }, mesh = {Alleles ; Animals ; Base Sequence ; Fossils ; Gene Flow ; Gene Library ; *Genetic Variation ; Genome, Human/*genetics ; *Heterozygote ; Humans ; Molecular Sequence Data ; Neanderthals/*genetics ; Sequence Analysis, DNA ; }, abstract = {We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.}, }
@article {pmid22910914, year = {2012}, author = {Denisova, OV and Kakkola, L and Feng, L and Stenman, J and Nagaraj, A and Lampe, J and Yadav, B and Aittokallio, T and Kaukinen, P and Ahola, T and Kuivanen, S and Vapalahti, O and Kantele, A and Tynell, J and Julkunen, I and Kallio-Kokko, H and Paavilainen, H and Hukkanen, V and Elliott, RM and De Brabander, JK and Saelens, X and Kainov, DE}, title = {Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza a virus infection.}, journal = {The Journal of biological chemistry}, volume = {287}, number = {42}, pages = {35324-35332}, doi = {10.1074/jbc.M112.392142}, pmid = {22910914}, issn = {1083-351X}, support = {P01 CA095471/CA/NCI NIH HHS/United States ; R01 CA090349/CA/NCI NIH HHS/United States ; CA90349/CA/NCI NIH HHS/United States ; CA95471/CA/NCI NIH HHS/United States ; }, mesh = {Amides/*pharmacology ; Animals ; Antiviral Agents/*pharmacology ; Cercopithecus aethiops ; Deoxycytidine/*analogs & derivatives/pharmacology ; Dogs ; Humans ; Influenza A Virus, H3N2 Subtype/*drug effects/*physiology ; Influenza, Human/*drug therapy/metabolism ; Myeloid Cell Leukemia Sequence 1 Protein ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/metabolism ; Pyrroles/*pharmacology ; RNA, Viral/biosynthesis ; Salicylates/*pharmacology ; Vero Cells ; Virus Replication ; }, abstract = {Influenza A viruses (IAVs) infect humans and cause significant morbidity and mortality. Different treatment options have been developed; however, these were insufficient during recent IAV outbreaks. Here, we conducted a targeted chemical screen in human nonmalignant cells to validate known and search for novel host-directed antivirals. The screen validated saliphenylhalamide (SaliPhe) and identified two novel anti-IAV agents, obatoclax and gemcitabine. Further experiments demonstrated that Mcl-1 (target of obatoclax) provides a novel host target for IAV treatment. Moreover, we showed that obatoclax and SaliPhe inhibited IAV uptake and gemcitabine suppressed viral RNA transcription and replication. These compounds possess broad spectrum antiviral activity, although their antiviral efficacies were virus-, cell type-, and species-specific. Altogether, our results suggest that phase II obatoclax, investigational SaliPhe, and FDA/EMEA-approved gemcitabine represent potent antiviral agents.}, }
@article {pmid22883142, year = {2012}, author = {Mendez, FL and Watkins, JC and Hammer, MF}, title = {A haplotype at STAT2 Introgressed from neanderthals and serves as a candidate of positive selection in Papua New Guinea.}, journal = {American journal of human genetics}, volume = {91}, number = {2}, pages = {265-274}, doi = {10.1016/j.ajhg.2012.06.015}, pmid = {22883142}, issn = {1537-6605}, mesh = {Adaptation, Biological/genetics ; Animals ; Base Sequence ; Evolution, Molecular ; Gene Components ; *Genetics, Population ; Genotype ; Haplotypes/*genetics ; Humans ; Linkage Disequilibrium ; Molecular Sequence Data ; Mutation/genetics ; Neanderthals/*genetics ; Papua New Guinea ; *Phylogeny ; Receptor, ErbB-3/genetics ; STAT2 Transcription Factor/*genetics ; *Selection, Genetic ; Sequence Analysis, DNA ; }, abstract = {Signals of archaic admixture have been identified through comparisons of the draft Neanderthal and Denisova genomes with those of living humans. Studies of individual loci contributing to these genome-wide average signals are required for characterization of the introgression process and investigation of whether archaic variants conferred an adaptive advantage to the ancestors of contemporary human populations. However, no definitive case of adaptive introgression has yet been described. Here we provide a DNA sequence analysis of the innate immune gene STAT2 and show that a haplotype carried by many Eurasians (but not sub-Saharan Africans) has a sequence that closely matches that of the Neanderthal STAT2. This haplotype, referred to as N, was discovered through a resequencing survey of the entire coding region of STAT2 in a global sample of 90 individuals. Analyses of publicly available complete genome sequence data show that haplotype N shares a recent common ancestor with the Neanderthal sequence (~80 thousand years ago) and is found throughout Eurasia at an average frequency of ~5%. Interestingly, N is found in Melanesian populations at ~10-fold higher frequency (~54%) than in Eurasian populations. A neutrality test that controls for demography rejects the hypothesis that a variant of N rose to high frequency in Melanesia by genetic drift alone. Although we are not able to pinpoint the precise target of positive selection, we identify nonsynonymous mutations in ERBB3, ESYT1, and STAT2-all of which are part of the same 250 kb introgressive haplotype-as good candidates.}, }
@article {pmid22810113, year = {2012}, author = {Malyarchuk, BA and Derenko, M and Denisova, G}, title = {On the Y-chromosome haplogroup C3c classification.}, journal = {Journal of human genetics}, volume = {57}, number = {10}, pages = {685-686}, doi = {10.1038/jhg.2012.93}, pmid = {22810113}, issn = {1435-232X}, mesh = {Chromosomes, Human, Y/*genetics ; Ethnic Groups/*genetics ; Europe, Eastern ; Far East ; Genetic Markers ; Genetics, Population/*methods ; *Haplotypes ; Humans ; Male ; Minisatellite Repeats ; Mutation ; Phylogeny ; Polymorphism, Single Nucleotide ; Siberia ; }, abstract = {As there are ambiguities in classification of the Y-chromosome haplogroup C3c, relatively frequent in populations of Northern Asia, we analyzed all three haplogroup-defining markers M48, M77 and M86 in C3-M217-individuals from Siberia, Eastern Asia and Eastern Europe. We have found that haplogroup C3c is characterized by the derived state at M48, whereas mutations at both M77 and M86 define subhaplogroup C3c1. The branch defined by M48 alone would belong to subhaplogroup C3c*, characteristic for some populations of Central and Eastern Siberia, such as Koryaks, Evens, Evenks and Yukaghirs. Subhaplogroup C3c* individuals could be considered as remnants of the Neolithic population of Siberia, based on the age of C3c*-short tandem repeat variation amounting to 4.5 ± 2.4 thousand years.}, }
@article {pmid22808780, year = {2012}, author = {Malanicheva, TG and Ziatdinova, NV and Denisova, SN}, title = {[Prevalence and risk factors of gastroduodenal and biliary system diseases in infants and preschool children].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {1}, pages = {55-58}, pmid = {22808780}, issn = {1682-8658}, mesh = {Age Factors ; *Biliary Tract Diseases/diagnosis/epidemiology/etiology ; Child ; Child, Preschool ; *Duodenal Diseases/diagnosis/epidemiology/etiology ; Humans ; Infant ; Mass Screening ; Prevalence ; Risk Factors ; Russia/epidemiology ; *Stomach Diseases/diagnosis/epidemiology/etiology ; }, abstract = {Gastroduodenal pathology, functional disorders and inflammatory diseases of the biliary tract take leading position among the diseases of the digestive system in children. Precisely these clinical forms are more intensive then other nosology. Continuous screening questionnaire of 786 children aged 1.5 to 7 years was carried out to study the prevalence and risk factors for diseases of the digestive system in children. Based on retrieved data was determined that 47,1 +/- 3,5% of children had symptoms of gastro-intestinal tract and biliary system diseases. They met 2.3 times more often in children aged 4 to 7 years, than in children from 1.5 to 3 years old. Immerced examination revealed that the incidence of dyskinesia of the biliary tract was 33 +/- 3,3%, chronic gastritis (CG) and gastroduodenitis (GDD)--6,2 +/- 1,8%, chronic cholecystitis--4,2 +/- 1,4%, functional disorders of the stomach (FGD)--2,8 +/- 1,2% and duodenal ulcer (DU)--0,3 +/- 0,4% of cases. In the structure of digestive diseases in children from 1.5 to 7 years in the first place were DBT--70%, the second--CGD and CG--14.7%--the third chronic cholecystitis--8.9%, the fourth--FGD--5.9% and in fifth place--DU-0.5% of cases. At the care record in the pediatric clinic with diseases of the digestive system were registered only 7,9 +/- 1,9% of children, which is 5.9 times lower accordinig to data of active diagnostic. The leading medical and social risk factors and their complex influence on the formation of digestive diseases in infants and preschool children.}, }
@article {pmid22781494, year = {2012}, author = {Belousov, AB and Wang, Y and Song, JH and Denisova, JV and Berman, NE and Fontes, JD}, title = {Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.}, journal = {Neuroscience letters}, volume = {524}, number = {1}, pages = {16-19}, doi = {10.1016/j.neulet.2012.06.065}, pmid = {22781494}, issn = {1872-7972}, support = {P30 HD002528/HD/NICHD NIH HHS/United States ; R01 NS064256/NS/NINDS NIH HHS/United States ; R21 NS076925/NS/NINDS NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Brain/metabolism/*pathology ; Brain Injuries/metabolism/*pathology ; Cell Death ; Cerebral Cortex/metabolism/pathology ; Connexins/*genetics ; Gap Junctions/drug effects/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/pathology/*physiology ; Receptors, Metabotropic Glutamate/antagonists & inhibitors ; }, abstract = {In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death.}, }
@article {pmid22702107, year = {2012}, author = {Bugaeva, LI and Denisova, TD and Spasov, AA}, title = {[Effect of ladasten on antenatal and postnatal development].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {75}, number = {4}, pages = {23-25}, pmid = {22702107}, issn = {0869-2092}, mesh = {Adamantane/administration & dosage/*analogs & derivatives ; Animals ; Female ; Fetal Development/*drug effects ; Pregnancy ; Rats ; Weight Gain/*drug effects ; }, abstract = {Positive effects of ladasten on both antenatal and postnatal development have been established in experiments on pregnant female rats. Under the action of this drug, the number of resorption events decreases and process of antenatal development of fetuses is activated. In the postnatal period, increased weight gain and accelerated physical development has been observed in the progeny of rats treated with ladasten.}, }
@article {pmid22686063, year = {2012}, author = {Kul'bitskiĭ, BN and Larev, ZV and Fedulova, MV and Denisova, OP and Bogomolov, DV}, title = {[Pathology of the heart conducting system in the thanatogenesis of sudden death from alcoholic cardiomyopathy and coronary heart disease].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {55}, number = {2}, pages = {62-65}, pmid = {22686063}, issn = {0039-4521}, mesh = {Cardiomyopathy, Alcoholic/complications/*pathology ; Coronary Disease/complications/*pathology ; Death, Sudden/etiology/*pathology ; *Forensic Pathology ; Heart Conduction System/*pathology ; Humans ; Thanatology ; }, abstract = {The present literature review is focused on the contribution of various pathological changes in the heart conducting system to the tanatogenesis of sudden death from alcoholic cardiomyopathy and coronary heart disease viewed from the perspective of a forensic medical expert. The currently available data on the disorders in the heart conducting system in the subjects with these diseases are presented. Various aspects of pathology of the heart conducting system are considered in the modern and historical contexts. The prospects for the further investigations into the tanatogenic mechanisms of sudden death by reason of alcoholic cardiomyopathy and coronary heart disease are outlined.}, }
@article {pmid22686058, year = {2012}, author = {Denisova, OP and Kul'bitskiĭ, BN and Putintsev, VA and Bogomolova, IN and Bogomolov, DV}, title = {[Characteristics of morphological manifestations of anaphylactic shock in response to the administration of pharmaceutical preparations encountered in the practice of forensic medical expert-histologist].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {55}, number = {2}, pages = {46-49}, pmid = {22686058}, issn = {0039-4521}, mesh = {Adult ; Anaphylaxis/chemically induced/*pathology ; *Drug-Related Side Effects and Adverse Reactions ; *Expert Testimony ; Fatal Outcome ; Female ; *Forensic Pathology ; *Forensic Toxicology ; Government Agencies ; *Histology ; Humans ; Male ; Pharmaceutical Preparations/administration & dosage/*classification ; Pregnancy ; Young Adult ; }, abstract = {The authors report the results of a forensic medical investigation of 6 cases of death associated with the administration of pharmaceutical products documented by forensic medical experts of the Russian Centre of Forensic Medical Expertise. The results of the study are compared with the clinical data and summarized using the methods of tanatogenetic analysis. The following main clinical variants of iatrogenic anaphylactic shock (IAS) are distinguished: bronchospastic IAS (n = 1), asphyxic IAS (n = 1), hemodynamic IAS (n = 3), and combined (bronchospastic plus hemodynamic) IAS (n = 1). The signs of all these variants are described allowing for their diagnostics and differentiation diagnostics. These data can be used for the purpose of forensic medical diagnostics and elucidation of the mechanisms of tanatogenesis.}, }
@article {pmid22677281, year = {2012}, author = {Agoni, L and Golden, A and Guha, C and Lenz, J}, title = {Neandertal and Denisovan retroviruses.}, journal = {Current biology : CB}, volume = {22}, number = {11}, pages = {R437-8}, doi = {10.1016/j.cub.2012.04.049}, pmid = {22677281}, issn = {1879-0445}, support = {EB009040/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Humans ; Molecular Sequence Data ; Neanderthals/*genetics/virology ; Retroviridae/*genetics ; }, }
@article {pmid22665810, year = {2012}, author = {Wang, X and Mitra, N and Secundino, I and Banda, K and Cruz, P and Padler-Karavani, V and Verhagen, A and Reid, C and Lari, M and Rizzi, E and Balsamo, C and Corti, G and De Bellis, G and Longo, L and , and Beggs, W and Caramelli, D and Tishkoff, SA and Hayakawa, T and Green, ED and Mullikin, JC and Nizet, V and Bui, J and Varki, A}, title = {Specific inactivation of two immunomodulatory SIGLEC genes during human evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {25}, pages = {9935-9940}, doi = {10.1073/pnas.1119459109}, pmid = {22665810}, issn = {1091-6490}, support = {DP1 ES022577/ES/NIEHS NIH HHS/United States ; P01 HL107150/HL/NHLBI NIH HHS/United States ; R01 HD051796/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Deletion ; *Gene Silencing ; Humans ; Immune System ; Lectins/*genetics ; Primates ; Sialic Acid Binding Immunoglobulin-like Lectins ; }, abstract = {Sialic acid-recognizing Ig-like lectins (Siglecs) are signaling receptors that modulate immune responses, and are targeted for interactions by certain pathogens. We describe two primate Siglecs that were rendered nonfunctional by single genetic events during hominin evolution after our common ancestor with the chimpanzee. SIGLEC13 was deleted by an Alu-mediated recombination event, and a single base pair deletion disrupted the ORF of SIGLEC17. Siglec-13 is expressed on chimpanzee monocytes, innate immune cells that react to bacteria. The human SIGLEC17P pseudogene mRNA is still expressed at high levels in human natural killer cells, which bridge innate and adaptive immune responses. As both resulting pseudogenes are homozygous in all human populations, we resurrected the originally encoded proteins and examined their functions. Chimpanzee Siglec-13 and the resurrected human Siglec-17 recruit a signaling adapter and bind sialic acids. Expression of either Siglec in innate immune cells alters inflammatory cytokine secretion in response to Toll-like receptor-4 stimulation. Both Siglecs can also be engaged by two potentially lethal sialylated bacterial pathogens of newborns and infants, agents with a potential impact on reproductive fitness. Neanderthal and Denisovan genomes show human-like sequences at both loci, corroborating estimates that the initial pseudogenization events occurred in the common ancestral population of these hominins. Both loci also show limited polymorphic diversity, suggesting selection forces predating the origin of modern humans. Taken together, these data suggest that genetic elimination of Siglec-13 and/or Siglec-17 represents signatures of infectious and/or other inflammatory selective processes contributing to population restrictions during hominin origins.}, }
@article {pmid22412940, year = {2012}, author = {Burbano, HA and Green, RE and Maricic, T and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Kelso, J and Pollard, KS and Lachmann, M and Pääbo, S}, title = {Analysis of human accelerated DNA regions using archaic hominin genomes.}, journal = {PloS one}, volume = {7}, number = {3}, pages = {e32877}, doi = {10.1371/journal.pone.0032877}, pmid = {22412940}, issn = {1932-6203}, support = {R01 GM082901/GM/NIGMS NIH HHS/United States ; GM082901/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Biological/genetics ; Animals ; Cluster Analysis ; DNA/chemistry ; Evolution, Molecular ; *Genome ; *Genome, Human ; Hominidae/*genetics ; Humans ; Male ; Mutation ; Neanderthals/genetics ; }, abstract = {Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations.}, }
@article {pmid22393781, year = {2011}, author = {Maliarchuk, BA}, title = {[Adaptive evolution of the Homo mitochondrial genome].}, journal = {Molekuliarnaia biologiia}, volume = {45}, number = {5}, pages = {845-850}, pmid = {22393781}, issn = {0026-8984}, mesh = {Adaptation, Biological/*genetics ; Amino Acid Sequence ; Amino Acid Substitution/*genetics ; Animals ; *Biological Evolution ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/*genetics/metabolism ; Genes, Mitochondrial ; *Genome, Mitochondrial ; Hominidae/*genetics ; Humans ; Molecular Sequence Data ; Neanderthals/*genetics ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {Adaptive evolution of 12 protein-coding mitochondrial genes in members of genus Homo (Denisova hominin (H. sp. Altai), Neandertals (H. neanderthalensis) and modern humans (H. sapiens)) has been evaluated by assessing the pattern of changes in the physicochemical properties of amino acid replacements during the primate evolution. It has been found that in the Homo molecular adaptation (positive destabilizing selection) become apparent in the form of 12 radical amino acid replacements accompanied by statistically significant (P < 0.001) changes of physicochemical properties that probably had the functional consequences. These replacements have occurred on the stage of a common ancestor of the Homo (in CO2 and CytB genes) as well as with the appearance of the common ancestor of Neandertals and modern humans (in CO1 and ND5 genes). Radical amino acid replacements were mainly revealed in the cytochrome c oxidase complex IV and cytochrome bc1 complex III, thus coinciding with general trend of increasing of non-synonymous changes in mtDNA genes coding subunits of complexes III and IV proteins in anthropoid primates.}, }
@article {pmid22363811, year = {2012}, author = {Derenko, M and Malyarchuk, B and Denisova, G and Perkova, M and Rogalla, U and Grzybowski, T and Khusnutdinova, E and Dambueva, I and Zakharov, I}, title = {Complete mitochondrial DNA analysis of eastern Eurasian haplogroups rarely found in populations of northern Asia and eastern Europe.}, journal = {PloS one}, volume = {7}, number = {2}, pages = {e32179}, doi = {10.1371/journal.pone.0032179}, pmid = {22363811}, issn = {1932-6203}, mesh = {Asia ; Asian Continental Ancestry Group/*genetics ; DNA, Mitochondrial/*genetics ; Ethnic Groups/*genetics ; Europe ; European Continental Ancestry Group/*genetics ; Genetic Variation ; *Genetics, Population ; Haplotypes/*genetics ; Humans ; Molecular Sequence Data ; Phylogeny ; Phylogeography ; Principal Component Analysis ; }, abstract = {With the aim of uncovering all of the most basal variation in the northern Asian mitochondrial DNA (mtDNA) haplogroups, we have analyzed mtDNA control region and coding region sequence variation in 98 Altaian Kazakhs from southern Siberia and 149 Barghuts from Inner Mongolia, China. Both populations exhibit the prevalence of eastern Eurasian lineages accounting for 91.9% in Barghuts and 60.2% in Altaian Kazakhs. The strong affinity of Altaian Kazakhs and populations of northern and central Asia has been revealed, reflecting both influences of central Asian inhabitants and essential genetic interaction with the Altai region indigenous populations. Statistical analyses data demonstrate a close positioning of all Mongolic-speaking populations (Mongolians, Buryats, Khamnigans, Kalmyks as well as Barghuts studied here) and Turkic-speaking Sojots, thus suggesting their origin from a common maternal ancestral gene pool. In order to achieve a thorough coverage of DNA lineages revealed in the northern Asian matrilineal gene pool, we have completely sequenced the mtDNA of 55 samples representing haplogroups R11b, B4, B5, F2, M9, M10, M11, M13, N9a and R9c1, which were pinpointed from a massive collection (over 5000 individuals) of northern and eastern Asian, as well as European control region mtDNA sequences. Applying the newly updated mtDNA tree to the previously reported northern Asian and eastern Asian mtDNA data sets has resolved the status of the poorly classified mtDNA types and allowed us to obtain the coalescence age estimates of the nodes of interest using different calibrated rates. Our findings confirm our previous conclusion that northern Asian maternal gene pool consists of predominantly post-LGM components of eastern Asian ancestry, though some genetic lineages may have a pre-LGM/LGM origin.}, }
@article {pmid22343905, year = {2012}, author = {Xu, C and Schmidt, WU and Galinovic, I and Villringer, K and Hotter, B and Ostwaldt, AC and Denisova, N and Kellner, E and Kiselev, V and Fiebach, JB}, title = {The potential of microvessel density in prediction of infarct growth: a two-month experimental study in vessel size imaging.}, journal = {Cerebrovascular diseases (Basel, Switzerland)}, volume = {33}, number = {4}, pages = {303-309}, doi = {10.1159/000335302}, pmid = {22343905}, issn = {1421-9786}, mesh = {Aged ; Aged, 80 and over ; Blood Circulation Time ; Cerebral Infarction/*pathology ; Cohort Studies ; Data Interpretation, Statistical ; Diffusion Magnetic Resonance Imaging ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Angiography ; Male ; Microvessels/*pathology ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Reperfusion Injury/pathology ; Tissue Plasminogen Activator/therapeutic use ; }, abstract = {OBJECTIVES: Vessel size imaging is a novel technique to evaluate pathological changes of the microvessel density quantity Q and the mean vessel size index (VSI). As a follow-up study, we assessed these parameters for microscopic description of ischemic penumbra and their potentials in predicting lesion growth.

METHODS: Seventy-five patients with a perfusion-diffusion mismatch were examined within 24 h from symptom onset. We defined three regions of interest: the initial infarct (INF), the ischemic penumbra (IPE), and the healthy region (HEA) symmetric to the IPE. For 23 patients with a 6th-day follow-up, IPE regions were divided into areas of infarct growth and areas of oligemia.

RESULT: The median values of Q and VSI were: for INF 0.29 s(-1/3) and 15.8 μm, for IPE 0.33 s(-1/3) and 20.6 μm and for HEA 0.36 s(-1/3) and 17.4 μm. The Q in the IPE was significantly smaller than in HEA, and VSI was significantly larger. The Q with a threshold of 0.32 s(-1/3) predicted the final infarction with a sensitivity of 69% and a specificity of 64%.

CONCLUSIONS: The reduced Q and increased VSI in the IPE confirmed our previous pilot results. Although Q showed a trend to identify the severity of ischemia in an overall voxel population, its potential in predicting infarct growth needs to be further tested in a larger cohort including a clear status of reperfusion and recanalization.}, }
@article {pmid22334930, year = {2011}, author = {Denisova, OA and Titarova, LS}, title = {[The atypical course of subperiosteal abscess of the orbital wall].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {5}, pages = {66-67}, pmid = {22334930}, issn = {0042-4668}, mesh = {Abscess/*pathology ; Anti-Bacterial Agents/administration & dosage ; Child ; Endoscopy/*methods ; Female ; Fibrinolytic Agents/administration & dosage ; Humans ; Leeching/methods ; *Maxillary Sinusitis/diagnostic imaging/etiology/physiopathology ; Nasal Bone/abnormalities ; *Nasal Obstruction/complications/congenital/diagnosis/physiopathology ; Orbit/*pathology ; *Orbital Diseases/diagnosis/etiology/physiopathology/therapy ; Punctures ; Radiography ; Rhinoplasty/*methods ; Treatment Outcome ; Turbinates/abnormalities ; }, abstract = {The authors describe a clinical case of malformation of intranasal structures of the lateral wall and the middle turbinated bone of the nose (bullous middle turbinated bone, lateral position of the middle turbinated bone, hypertrophy of ethmoidal bulla and uncinate process) in combination with expressed deformation of the nasal septum. These malformations were responsible for the development of acute hemisinusitis complicated by subperiosteal abscess of the superomedial orbital wall. Conjunctival chemosis was impossible to remove by traditional medicamental therapy and surgical intervention. Hirudotherapy produced the well-apparent anti-odematous, anti-inflammatory, anti-coagulative, and thrombolytic effects that resulted in reduced conjunctival oedema and marked positive dynamics of the state of the eyeball. Subcutaneous administration of anticoagulants was used to prevent thrombosis of orbital veins and cerebral venous sinuses.}, }
@article {pmid22319157, year = {2012}, author = {Mendez, FL and Watkins, JC and Hammer, MF}, title = {Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations.}, journal = {Molecular biology and evolution}, volume = {29}, number = {6}, pages = {1513-1520}, doi = {10.1093/molbev/msr301}, pmid = {22319157}, issn = {1537-1719}, mesh = {2',5'-Oligoadenylate Synthetase/*genetics ; 5' Untranslated Regions/genetics ; African Continental Ancestry Group/*genetics ; Animals ; Asian Continental Ancestry Group/genetics ; Chromosomes, Human, Pair 12/genetics ; Genetic Speciation ; Genotyping Techniques ; Haplotypes ; Hominidae/genetics ; Humans ; *Hybridization, Genetic ; Linkage Disequilibrium ; Melanesia ; Models, Genetic ; Oceanic Ancestry Group/genetics ; *Polymorphism, Genetic ; Sequence Analysis, DNA ; }, abstract = {Recent analysis of DNA extracted from two Eurasian forms of archaic human shows that more genetic variants are shared with humans currently living in Eurasia than with anatomically modern humans in sub-Saharan Africa. Although these genome-wide average measures of genetic similarity are consistent with the hypothesis of archaic admixture in Eurasia, analyses of individual loci exhibiting the signal of archaic introgression are needed to test alternative hypotheses and investigate the admixture process. Here, we provide a detailed sequence analysis of the innate immune gene OAS1, a locus with a divergent Melanesian haplotype that is very similar to the Denisova sequence from the Altai region of Siberia. We resequenced a 7-kb region encompassing the OAS1 gene in 88 individuals from six Old World populations (San, Biaka, Mandenka, French Basque, Han Chinese, and Papua New Guineans) and discovered previously unknown and ancient genetic variation. The 5' region of this gene has unusual patterns of diversity, including 1) higher levels of nucleotide diversity in Papuans than in sub-Saharan Africans, 2) very deep ancestry with an estimated time to the most recent common ancestor of >3 myr, and 3) a basal branching pattern with Papuan individuals on either side of the rooted network. A global geographic survey of >1,500 individuals showed that the divergent Papuan haplotype is nearly restricted to populations from eastern Indonesia and Melanesia. Polymorphic sites within this haplotype are shared with the draft Denisova genome over a span of ∼90 kb and are associated with an extended block of linkage disequilibrium, supporting the hypothesis that this haplotype introgressed from an archaic source that likely lived in Eurasia.}, }
@article {pmid22238107, year = {2012}, author = {Wang, Y and Song, JH and Denisova, JV and Park, WM and Fontes, JD and Belousov, AB}, title = {Neuronal gap junction coupling is regulated by glutamate and plays critical role in cell death during neuronal injury.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {32}, number = {2}, pages = {713-725}, doi = {10.1523/JNEUROSCI.3872-11.2012}, pmid = {22238107}, issn = {1529-2401}, support = {R01 NS064256/NS/NINDS NIH HHS/United States ; R01 NS064256-02/NS/NINDS NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; R01 NS064256-01A1/NS/NINDS NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Brain Ischemia/*pathology/physiopathology ; Cell Death/physiology ; Cells, Cultured ; Cerebral Cortex/cytology ; Connexins/genetics/physiology ; Gap Junctions/*physiology ; Glutamic Acid/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/pathology/*physiology ; }, abstract = {In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI), and epilepsy. The coupling of neurons by gap junctions (electrical synapses) increases during neuronal injury. We report here that the ischemic increase in neuronal gap junction coupling is regulated by glutamate via group II metabotropic glutamate receptors (mGluRs). Specifically, using electrotonic coupling, Western blots, and siRNA in the mouse somatosensory cortex in vivo and in vitro, we demonstrate that activation of group II mGluRs increases background levels of neuronal gap junction coupling and expression of connexin 36 (Cx36) (neuronal gap junction protein), and inactivation of group II mGluRs prevents the ischemia-mediated increases in the coupling and Cx36 expression. We also show that the regulation is via cAMP/PKA (cAMP-dependent protein kinase)-dependent signaling and posttranscriptional control of Cx36 expression and that other glutamate receptors are not involved in these regulatory mechanisms. Furthermore, using the analysis of neuronal death, we show that inactivation of group II mGluRs or genetic elimination of Cx36 both dramatically reduce ischemia-mediated neuronal death in vitro and in vivo. Similar results are obtained using in vitro models of TBI and epilepsy. Our results indicate that neuronal gap junction coupling is a critical component of glutamate-dependent neuronal death. They also suggest that causal link among group II mGluR function, neuronal gap junction coupling, and neuronal death has a universal character and operates in different types of neuronal injuries.}, }
@article {pmid22224240, year = {2011}, author = {Morgunov, LIu and Denisova, IA and Rozhkova, TI and Stakhovskaia, LV and Skvortsova, VI}, title = {[Androgenic deficit and its treatment in stroke male patients with diabetes mellitus type II].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {111}, number = {8 Pt 2}, pages = {21-24}, pmid = {22224240}, issn = {1997-7298}, mesh = {Aged ; Androgens/*deficiency ; Diabetes Mellitus, Type 2/*metabolism ; *Hormone Replacement Therapy ; Humans ; Male ; Middle Aged ; Stroke/*metabolism ; Testosterone/administration & dosage/*analogs & derivatives ; }, abstract = {We have studied 154 men (mean age 61,4+/-4,1 years) with the first hemispheric ischemic stroke. Clinical and laboratory studies have revealed the androgenic deficit in 66,3%, with its frequency higher in patients with diabetes mellitus type II (50 and 26,3%, respectively). Forty-two men with diabetes mellitus type II and acquired androgenic deficit received replacing treatment with testosterone undecanoate in dose 1000 mg intramuscular. The treatment was started one week after the development of stroke, the next injections were given after 6 weeks and then every 12 weeks during 2 years. The control group included 30 males who did not receive androgens. After 2 years from the beginning of treatment, there were the decrease in clinical severity of androgenic deficit, the increase of total and free testosterone levels, and muscle power in the main group compared to the controls. Body mass index, glicated hemoglobin, cholesterol, triglycerides, low density lipoproteins have decreased as well. Secondary stroke has developed in 3 (7,1%) patients of the main group and in 5 (16,6%) controls; 12 (28,6%) patients returned to work in the main group compared to 2 (6,6%) in the control group. The treatment with androgens has a positive effect on risk factors of secondary ischemic stroke. It is an effective method for improvement of social adaptation of men survived after the stroke.}, }
@article {pmid22192823, year = {2011}, author = {Lalueza-Fox, C and Gilbert, MT}, title = {Paleogenomics of archaic hominins.}, journal = {Current biology : CB}, volume = {21}, number = {24}, pages = {R1002-9}, doi = {10.1016/j.cub.2011.11.021}, pmid = {22192823}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Demography ; *Evolution, Molecular ; Fossils ; Gene Flow ; Genetic Variation ; Genome, Human ; Hominidae/anatomy & histology/*genetics/physiology ; Humans/anatomy & histology/genetics/physiology ; Neanderthals/anatomy & histology/*genetics/physiology ; Phylogeny ; Species Specificity ; }, abstract = {In order to understand the genetic basis for the evolutionary success of modern humans, it is necessary to compare their genetic makeup to that of closely related species. Unfortunately, our closest living relatives, the chimpanzees, are evolutionarily quite distant. With the advent of ancient DNA study and more recently paleogenomics - the study of the genomes of ancient organisms - it has become possible to compare human genomes to those of much more closely related groups. Our closest known relatives are the Neanderthals, which evolved and lived in Europe and Western Asia, from about 600,000 years ago until their disappearance around 30,000 years ago following the expansion of anatomically modern humans into their range. The closely related Denisovans are only known by virtue of their DNA, which has been extracted from bone fragments dating around 30,000 to 50,000 years ago found in a single Siberian cave. Analyses of Neanderthal and Denisovan nuclear and mitochondrial genomes have revealed surprising insights into these archaic humans as well as our own species. The genomes provide a preliminary catalogue of derived amino acids that are specific to all extant modern humans, thus offering insights into the functional differences between the three lineages. In addition, the genomes provide evidence of gene flow between the three lineages after anatomically modern humans left Africa, drastically changing our view of human evolution.}, }
@article {pmid22042846, year = {2011}, author = {Skoglund, P and Jakobsson, M}, title = {Archaic human ancestry in East Asia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, number = {45}, pages = {18301-18306}, doi = {10.1073/pnas.1108181108}, pmid = {22042846}, issn = {1091-6490}, mesh = {Asia ; *Fossils ; Genetic Drift ; Genotype ; History, Ancient ; Humans ; Principal Component Analysis ; }, abstract = {Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia ("Denisovans") and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome--a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova-related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed.}, }
@article {pmid21944045, year = {2011}, author = {Reich, D and Patterson, N and Kircher, M and Delfin, F and Nandineni, MR and Pugach, I and Ko, AM and Ko, YC and Jinam, TA and Phipps, ME and Saitou, N and Wollstein, A and Kayser, M and Pääbo, S and Stoneking, M}, title = {Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania.}, journal = {American journal of human genetics}, volume = {89}, number = {4}, pages = {516-528}, doi = {10.1016/j.ajhg.2011.09.005}, pmid = {21944045}, issn = {1537-6605}, mesh = {Animals ; Asia, Southeastern ; Biological Evolution ; DNA, Mitochondrial/genetics ; *Gene Flow ; Genotype ; Geography ; Hominidae/*genetics ; Humans ; Models, Genetic ; Models, Statistical ; Oceania ; Oceanic Ancestry Group ; Pan troglodytes ; Polymorphism, Single Nucleotide ; }, abstract = {It has recently been shown that ancestors of New Guineans and Bougainville Islanders have inherited a proportion of their ancestry from Denisovans, an archaic hominin group from Siberia. However, only a sparse sampling of populations from Southeast Asia and Oceania were analyzed. Here, we quantify Denisova admixture in 33 additional populations from Asia and Oceania. Aboriginal Australians, Near Oceanians, Polynesians, Fijians, east Indonesians, and Mamanwa (a "Negrito" group from the Philippines) have all inherited genetic material from Denisovans, but mainland East Asians, western Indonesians, Jehai (a Negrito group from Malaysia), and Onge (a Negrito group from the Andaman Islands) have not. These results indicate that Denisova gene flow occurred into the common ancestors of New Guineans, Australians, and Mamanwa but not into the ancestors of the Jehai and Onge and suggest that relatives of present-day East Asians were not in Southeast Asia when the Denisova gene flow occurred. Our finding that descendants of the earliest inhabitants of Southeast Asia do not all harbor Denisova admixture is inconsistent with a history in which the Denisova interbreeding occurred in mainland Asia and then spread over Southeast Asia, leading to all its earliest modern human inhabitants. Instead, the data can be most parsimoniously explained if the Denisova gene flow occurred in Southeast Asia itself. Thus, archaic Denisovans must have lived over an extraordinarily broad geographic and ecological range, from Siberia to tropical Asia.}, }
@article {pmid21897868, year = {2011}, author = {Vorobieva, NV and Sherbakov, DY and Druzhkova, AS and Stanyon, R and Tsybankov, AA and Vasil'ev, SK and Shunkov, MV and Trifonov, VA and Graphodatsky, AS}, title = {Genotyping of Capreolus pygargus fossil DNA from Denisova cave reveals phylogenetic relationships between ancient and modern populations.}, journal = {PloS one}, volume = {6}, number = {8}, pages = {e24045}, doi = {10.1371/journal.pone.0024045}, pmid = {21897868}, issn = {1932-6203}, mesh = {Animals ; DNA/*genetics/isolation & purification ; Deer/*genetics ; *Evolution, Molecular ; *Fossils ; Genetic Variation ; *Genotyping Techniques ; Geology ; Haplotypes ; *Phylogeny ; Sequence Analysis, DNA ; Siberia ; }, abstract = {BACKGROUND: The extant roe deer (Capreolus Gray, 1821) includes two species: the European roe deer (C. capreolus) and the Siberian roe deer (C. pygargus) that are distinguished by morphological and karyotypical differences. The Siberian roe deer occupies a vast area of Asia and is considerably less studied than the European roe deer. Modern systematics of the Siberian roe deer remain controversial with 4 morphological subspecies. Roe deer fossilized bones are quite abundant in Denisova cave (Altai Mountains, South Siberia), where dozens of both extant and extinct mammalian species from modern Holocene to Middle Pleistocene have been retrieved.

We analyzed a 629 bp fragment of the mitochondrial control region from ancient bones of 10 Holocene and four Pleistocene Siberian roe deer from Denisova cave as well as 37 modern specimen belonging to populations from Altai, Tian Shan (Kyrgyzstan), Yakutia, Novosibirsk region and the Russian Far East. Genealogical reconstructions indicated that most Holocene haplotypes were probably ancestral for modern roe deer populations of Western Siberia and Tian Shan. One of the Pleistocene haplotypes was possibly ancestral for modern Yakutian populations, and two extinct Pleistocene haplotypes were close to modern roe deer from Tian Shan and Yakutia. Most modern geographical populations (except for West Siberian Plains) are heterogeneous and there is some tentative evidence for structure. However, we did not find any distinct phylogenetic signal characterizing particular subspecies in either modern or ancient samples.

METHODS: In this multicentre, randomized, parallel-group, double-blind, placebo-controlled study, patients with glycated haemoglobin (HbA1c) 7-11% and creatinine clearance <50 ml/min were stratified by baseline renal impairment (moderate, severe or end-stage on haemodialysis), and randomized (1 : 1) to saxagliptin 2.5 mg once daily or placebo for 12 weeks. Oral antihyperglycaemic drugs and insulin therapy present at enrolment were continued throughout the study. The absolute change in HbA1c from baseline to week 12 (primary efficacy end-point) was analysed using an analysis of covariance model with last observation carried forward methodology.

RESULTS: A total of 170 patients were randomized and treated. The adjusted mean decrease from baseline to week 12 in HbA1c was statistically significantly greater in the saxagliptin group than in the placebo group; the difference between treatments was -0.42% (95% confidence interval: -0.71 to -0.12%, p = 0.007). Adjusted mean HbA1c decreases from baseline to week 12 were numerically greater with saxagliptin than with placebo in the subgroups of patients with moderate (-0.64 vs. -0.05%) and severe (-0.95 vs. -0.50%) renal impairment. HbA1c reductions were similar between saxagliptin and placebo in the subgroup with end-stage renal disease on haemodialysis (-0.84 vs. -0.87%). Saxagliptin was generally well tolerated; incidences of adverse events and hypoglycaemic events were similar to placebo.

CONCLUSIONS: Saxagliptin 2.5 mg once daily is a well-tolerated treatment option for patients with inadequately controlled T2DM and renal impairment.}, }
@article {pmid21203537, year = {2010}, author = {Derenko, M and Malyarchuk, B and Grzybowski, T and Denisova, G and Rogalla, U and Perkova, M and Dambueva, I and Zakharov, I}, title = {Origin and post-glacial dispersal of mitochondrial DNA haplogroups C and D in northern Asia.}, journal = {PloS one}, volume = {5}, number = {12}, pages = {e15214}, doi = {10.1371/journal.pone.0015214}, pmid = {21203537}, issn = {1932-6203}, mesh = {Asia ; Asian Continental Ancestry Group/genetics ; DNA, Mitochondrial/*genetics ; Emigration and Immigration ; Female ; Genetic Variation ; Genetics, Population ; Haplotypes ; Humans ; Phylogeny ; *Phylogeography ; Sequence Analysis, DNA ; }, abstract = {More than a half of the northern Asian pool of human mitochondrial DNA (mtDNA) is fragmented into a number of subclades of haplogroups C and D, two of the most frequent haplogroups throughout northern, eastern, central Asia and America. While there has been considerable recent progress in studying mitochondrial variation in eastern Asia and America at the complete genome resolution, little comparable data is available for regions such as southern Siberia--the area where most of northern Asian haplogroups, including C and D, likely diversified. This gap in our knowledge causes a serious barrier for progress in understanding the demographic pre-history of northern Eurasia in general. Here we describe the phylogeography of haplogroups C and D in the populations of northern and eastern Asia. We have analyzed 770 samples from haplogroups C and D (174 and 596, respectively) at high resolution, including 182 novel complete mtDNA sequences representing haplogroups C and D (83 and 99, respectively). The present-day variation of haplogroups C and D suggests that these mtDNA clades expanded before the Last Glacial Maximum (LGM), with their oldest lineages being present in the eastern Asia. Unlike in eastern Asia, most of the northern Asian variants of haplogroups C and D began the expansion after the LGM, thus pointing to post-glacial re-colonization of northern Asia. Our results show that both haplogroups were involved in migrations, from eastern Asia and southern Siberia to eastern and northeastern Europe, likely during the middle Holocene.}, }
@article {pmid21179161, year = {2010}, author = {Reich, D and Green, RE and Kircher, M and Krause, J and Patterson, N and Durand, EY and Viola, B and Briggs, AW and Stenzel, U and Johnson, PL and Maricic, T and Good, JM and Marques-Bonet, T and Alkan, C and Fu, Q and Mallick, S and Li, H and Meyer, M and Eichler, EE and Stoneking, M and Richards, M and Talamo, S and Shunkov, MV and Derevianko, AP and Hublin, JJ and Kelso, J and Slatkin, M and Pääbo, S}, title = {Genetic history of an archaic hominin group from Denisova Cave in Siberia.}, journal = {Nature}, volume = {468}, number = {7327}, pages = {1053-1060}, doi = {10.1038/nature09710}, pmid = {21179161}, issn = {1476-4687}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; R01-GM40282/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asia ; DNA, Mitochondrial/genetics ; Europe ; Finger Phalanges/chemistry ; *Fossils ; *Gene Flow ; Genome/*genetics ; Hominidae/*classification/*genetics ; Humans ; Melanesia ; Molecular Sequence Data ; Phylogeny ; Siberia ; Tooth/anatomy & histology/chemistry ; }, abstract = {Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4-6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population 'Denisovans' and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.}, }
@article {pmid21129766, year = {2011}, author = {Martinón-Torres, M and Dennell, R and Bermúdez de Castro, JM}, title = {The Denisova hominin need not be an out of Africa story.}, journal = {Journal of human evolution}, volume = {60}, number = {2}, pages = {251-255}, doi = {10.1016/j.jhevol.2010.10.005}, pmid = {21129766}, issn = {1095-8606}, mesh = {Africa ; *Animal Migration ; Animals ; DNA, Mitochondrial/genetics ; Fossils ; Hominidae/*genetics ; Siberia ; }, }
@article {pmid21105351, year = {2010}, author = {Bogomil'skiĭ, MR and Garashchenko, TI and Denisova, OA}, title = {[Assessment of the effectiveness of sinuforte used for the combined treatment of rhinosinusitis and exudative otitis media in children].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {4}, pages = {74-77}, pmid = {21105351}, issn = {0042-4668}, mesh = {Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Combined Modality Therapy ; *Cyclamen ; Female ; Humans ; Male ; Otitis Media with Effusion/drug therapy/surgery/*therapy ; Phytotherapy ; Plant Extracts/*therapeutic use ; Rhinitis/drug therapy/surgery/*therapy ; Sinusitis/drug therapy/surgery/*therapy ; Treatment Outcome ; }, abstract = {The objective of the present study was to evaluate efficiency, safety, and tolerability of two single doses of sinuforte (INVAR, Russia) used in the combined treatment of rhinosinusitis (including that with concurrent exudative otitis media) in children at the age from 5 to 12 years. The data obtained suggest high efficiency of sinuforte in the treatment of mild and moderately severe acute rhinosinusitis and exudative otitis media. Inclusion of sinuforte in combined therapy of these conditions makes it possible to avoid drainage procedures and decreases duration of antibacterial treatment. Simultaneous acceleration of the recovery of functional activity of endonasal mucosa suggests pronounced anti-recurrent action of sinuforte.}, }
@article {pmid21067548, year = {2010}, author = {Denisova, GF and Denisov, DA and Bramson, JL}, title = {Applying bioinformatics for antibody epitope prediction using affinity-selected mimotopes - relevance for vaccine design.}, journal = {Immunome research}, volume = {6 Suppl 2}, number = {}, pages = {S6}, doi = {10.1186/1745-7580-6-S2-S6}, pmid = {21067548}, issn = {1745-7580}, abstract = {To properly characterize protective polyclonal antibody responses, it is necessary to examine epitope specificity. Most antibody epitopes are conformational in nature and, thus, cannot be identified using synthetic linear peptides. Cyclic peptides can function as mimetics of conformational epitopes (termed mimotopes), thereby providing targets, which can be selected by immunoaffinity purification. However, the management of large collections of random cyclic peptides is cumbersome. Filamentous bacteriophage provides a useful scaffold for the expression of random peptides (termed phage display) facilitating both the production and manipulation of complex peptide libraries. Immunoaffinity selection of phage displaying random cyclic peptides is an effective strategy for isolating mimotopes with specificity for a given antiserum. Further epitope prediction based on mimotope sequence is not trivial since mimotopes generally display only small homologies with the target protein. Large numbers of unique mimotopes are required to provide sufficient sequence coverage to elucidate the target epitope. We have developed a method based on pattern recognition theory to deal with the complexity of large collections of conformational mimotopes. The analysis consists of two phases: 1) The learning phase where a large collection of epitope-specific mimotopes is analyzed to identify epitope specific "signs" and 2) The identification phase where immunoaffinity-selected mimotopes are interrogated for the presence of the epitope specific "signs" and assigned to specific epitopes. We are currently using computational methods to define epitope "signs" without the need for prior knowledge of specific mimotopes. This technology provides an important tool for characterizing the breadth of antibody specificities within polyclonal antisera.}, }
@article {pmid20943940, year = {2010}, author = {Wang, Y and Denisova, JV and Kang, KS and Fontes, JD and Zhu, BT and Belousov, AB}, title = {Neuronal gap junctions are required for NMDA receptor-mediated excitotoxicity: implications in ischemic stroke.}, journal = {Journal of neurophysiology}, volume = {104}, number = {6}, pages = {3551-3556}, doi = {10.1152/jn.00656.2010}, pmid = {20943940}, issn = {1522-1598}, support = {HD-002528/HD/NICHD NIH HHS/United States ; P20 RR-024214/RR/NCRR NIH HHS/United States ; R01 DA-015088/DA/NIDA NIH HHS/United States ; R01 NS-064256/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Blood-Brain Barrier ; Brain Ischemia/chemically induced/*physiopathology ; Cells, Cultured/drug effects/physiology ; Connexins/deficiency ; Dentate Gyrus/drug effects/pathology ; Dizocilpine Maleate/pharmacology/therapeutic use ; Excitatory Amino Acid Antagonists/pharmacology/therapeutic use ; Gap Junctions/drug effects/*physiology ; Male ; Mefloquine/pharmacology/therapeutic use ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; N-Methylaspartate/pharmacokinetics/*toxicity ; Nerve Degeneration/*chemically induced/prevention & control ; Neurons/*physiology ; Neurotoxins/pharmacokinetics/*toxicity ; Patch-Clamp Techniques ; Photochemistry ; Receptors, N-Methyl-D-Aspartate/drug effects/*physiology ; Rose Bengal/radiation effects/toxicity ; }, abstract = {N-methyl-D-aspartate receptors (NMDARs) play an important role in cell survival versus cell death decisions during neuronal development, ischemia, trauma, and epilepsy. Coupling of neurons by electrical synapses (gap junctions) is high or increases in neuronal networks during all these conditions. In the developing CNS, neuronal gap junctions are critical for two different types of NMDAR-dependent cell death. However, whether neuronal gap junctions play a role in NMDAR-dependent neuronal death in the mature CNS was not known. Using Fluoro-Jade B staining, we show that a single intraperitoneal administration of NMDA (100 mg/kg) to adult wild-type mice induces neurodegeneration in three forebrain regions, including rostral dentate gyrus. However, the NMDAR-mediated neuronal death is prevented by pharmacological blockade of neuronal gap junctions (with mefloquine, 30 mg/kg) and does not occur in mice lacking neuronal gap junction protein, connexin 36. Using Western blots, electrophysiology, calcium imaging, and gas chromatography-mass spectrometry in wild-type and connexin 36 knockout mice, we show that the reduced level of neuronal death in knockout animals is not caused by the reduced expression of NMDARs, activity of NMDARs, or permeability of the blood-brain barrier to NMDA. In wild-type animals, this neuronal death is not caused by upregulation of connexin 36 by NMDA. Finally, pharmacological and genetic inactivation of neuronal gap junctions in mice also dramatically reduces neuronal death caused by photothrombotic focal cerebral ischemia. The results indicate that neuronal gap junctions are required for NMDAR-dependent excitotoxicity and play a critical role in ischemic neuronal death.}, }
@article {pmid20726964, year = {2010}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Wozniak, M and Grzybowski, T and Dambueva, I and Zakharov, I}, title = {Phylogeography of the Y-chromosome haplogroup C in northern Eurasia.}, journal = {Annals of human genetics}, volume = {74}, number = {6}, pages = {539-546}, doi = {10.1111/j.1469-1809.2010.00601.x}, pmid = {20726964}, issn = {1469-1809}, mesh = {Chromosomes, Human, Y/*genetics ; Ethnic Groups/genetics ; Europe, Eastern ; Far East ; Genetic Variation ; *Haplotypes ; Humans ; Male ; Microsatellite Repeats ; *Phylogeography ; Polymorphism, Single Nucleotide ; Siberia ; }, abstract = {To reconstruct the phylogenetic structure of Y-chromosome haplogroup (hg) C in populations of northern Eurasia, we have analyzed the diversity of microsatellite (STR) loci in a total sample of 413 males from 18 ethnic groups of Siberia, Eastern Asia and Eastern Europe. Analysis of SNP markers revealed that all Y-chromosomes studied belong to hg C3 and its subhaplogroups C3c and C3d, although some populations (such as Mongols and Koryaks) demonstrate a relatively high input (more than 30%) of yet unidentified C3* haplotypes. Median joining network analysis of STR haplotypes demonstrates that Y-chromosome gene pools of populations studied are characterized by the presence of DNA clusters originating from a limited number of frequent founder haplotypes. These are subhaplogroup C3d characteristic for Mongolic-speaking populations, "star cluster" in C3* paragroup, and a set of DYS19 duplicated C3c Y-chromosomes. All these DNA clusters show relatively recent coalescent times (less than 3000 years), so it is probable that founder effects, including social selection resulting in high male fertility associated with a limited number of paternal lineages, may explain the observed distribution of hg C3 lineages.}, }
@article {pmid20697660, year = {2010}, author = {Tarakina, NV and Neder, RB and Denisova, TA and Maksimova, LG and Baklanova, YV and Tyutyunnik, AP and Zubkov, VG}, title = {Defect crystal structure of new TiO(OH)2 hydroxide and related lithium salt Li2TiO3.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {39}, number = {35}, pages = {8168-8176}, doi = {10.1039/c0dt00354a}, pmid = {20697660}, issn = {1477-9234}, abstract = {Crystal structures of TiO(OH)(2) and Li(2)TiO(3) have been studied in detail and refined using X-ray powder diffraction data. Both compounds possess a high concentration of defects in the structure. The crystal structure of the Li(2)TiO(3) salt obtained at 700 degrees C reveals stacking faults of LiTi(2) metal layers, which leads to the appearance of short-range order in three possible space groups: C2/c, C2/m, P3(1)12. The possibility to stabilise this imperfect state increases the mobility of the Li(+) ions in the structure and allows the complete exchange of lithium by hydrogen in acid water solutions with formation of TiO(OH)(2). The crystal structure of TiO(OH)(2) belongs to the layered double hydroxide structure type with the 3R(1) sequence of oxygen layers and can be described as a stacking of charge-neutral metal oxyhydroxide slabs [(OH)(2)OTi(2)O(OH)(2)]. TiO(OH)(2) is the first layered double hydroxide structure formed by a cation with oxidation state +4 only.}, }
@article {pmid20488990, year = {2010}, author = {Gibson, DG and Glass, JI and Lartigue, C and Noskov, VN and Chuang, RY and Algire, MA and Benders, GA and Montague, MG and Ma, L and Moodie, MM and Merryman, C and Vashee, S and Krishnakumar, R and Assad-Garcia, N and Andrews-Pfannkoch, C and Denisova, EA and Young, L and Qi, ZQ and Segall-Shapiro, TH and Calvey, CH and Parmar, PP and Hutchison, CA and Smith, HO and Venter, JC}, title = {Creation of a bacterial cell controlled by a chemically synthesized genome.}, journal = {Science (New York, N.Y.)}, volume = {329}, number = {5987}, pages = {52-56}, doi = {10.1126/science.1190719}, pmid = {20488990}, issn = {1095-9203}, mesh = {Bacterial Proteins/analysis ; Base Sequence ; *Bioengineering ; Cloning, Molecular ; DNA, Bacterial/chemical synthesis/genetics ; Escherichia coli/genetics ; Gene Deletion ; Genes, Bacterial ; *Genetic Engineering ; *Genome, Bacterial ; Molecular Sequence Data ; Mycoplasma capricolum/*genetics ; Mycoplasma mycoides/*genetics/growth & development/physiology/ultrastructure ; Phenotype ; Plasmids ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Saccharomyces cerevisiae/genetics ; Transformation, Bacterial ; }, abstract = {We report the design, synthesis, and assembly of the 1.08-mega-base pair Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and its transplantation into a M. capricolum recipient cell to create new M. mycoides cells that are controlled only by the synthetic chromosome. The only DNA in the cells is the designed synthetic DNA sequence, including "watermark" sequences and other designed gene deletions and polymorphisms, and mutations acquired during the building process. The new cells have expected phenotypic properties and are capable of continuous self-replication.}, }
@article {pmid20457583, year = {2010}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Kravtsova, O}, title = {Mitogenomic diversity in Tatars from the Volga-Ural region of Russia.}, journal = {Molecular biology and evolution}, volume = {27}, number = {10}, pages = {2220-2226}, doi = {10.1093/molbev/msq065}, pmid = {20457583}, issn = {1537-1719}, mesh = {Base Sequence ; DNA, Mitochondrial/*genetics ; Ethnic Groups/*genetics ; Evolution, Molecular ; *Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; Humans ; Models, Genetic ; Molecular Sequence Data ; *Phylogeny ; Polymorphism, Restriction Fragment Length ; Russia ; Sequence Analysis, DNA ; }, abstract = {To investigate diversity of mitochondrial gene pool of Tatars inhabiting the territory of the middle Volga River basin, 197 individuals from two populations representing Kazan Tatars and Mishars were subjected for analysis of mitochondrial DNA (mtDNA) control region variation. In addition, 73 mitochondrial genomes of individuals from Mishar population were sequenced completely. It was found that mitochondrial gene pool of the Volga Tatars consists of two parts, but western Eurasian component prevails considerably (84% on average) over eastern Asian one (16%). Eastern Asian mtDNAs detected in Tatars belonged to a heterogeneous set of haplogroups (A, C, D, G, M7, M10, N9a, Y, and Z), although only haplogroups A and D were revealed simultaneously in both populations. Complete mtDNA variation study revealed that the age of western Eurasian haplogroups (such as U4, HV0a, and H) is less than 18,000 years, thus suggesting re-expansion of eastern Europeans soon after the Last Glacial Maximum.}, }
@article {pmid20336068, year = {2010}, author = {Krause, J and Fu, Q and Good, JM and Viola, B and Shunkov, MV and Derevianko, AP and Pääbo, S}, title = {The complete mitochondrial DNA genome of an unknown hominin from southern Siberia.}, journal = {Nature}, volume = {464}, number = {7290}, pages = {894-897}, doi = {10.1038/nature08976}, pmid = {20336068}, issn = {1476-4687}, mesh = {Africa/ethnology ; Animals ; DNA, Mitochondrial/*genetics/isolation & purification ; Emigration and Immigration ; Extinction, Biological ; Finger Phalanges ; Genome, Mitochondrial/*genetics ; Hominidae/*classification/*genetics ; Humans ; Molecular Sequence Data ; *Phylogeny ; Sequence Alignment ; Siberia ; Time Factors ; }, abstract = {With the exception of Neanderthals, from which DNA sequences of numerous individuals have now been determined, the number and genetic relationships of other hominin lineages are largely unknown. Here we report a complete mitochondrial (mt) DNA sequence retrieved from a bone excavated in 2008 in Denisova Cave in the Altai Mountains in southern Siberia. It represents a hitherto unknown type of hominin mtDNA that shares a common ancestor with anatomically modern human and Neanderthal mtDNAs about 1.0 million years ago. This indicates that it derives from a hominin migration out of Africa distinct from that of the ancestors of Neanderthals and of modern humans. The stratigraphy of the cave where the bone was found suggests that the Denisova hominin lived close in time and space with Neanderthals as well as with modern humans.}, }
@article {pmid20211840, year = {2010}, author = {Benders, GA and Noskov, VN and Denisova, EA and Lartigue, C and Gibson, DG and Assad-Garcia, N and Chuang, RY and Carrera, W and Moodie, M and Algire, MA and Phan, Q and Alperovich, N and Vashee, S and Merryman, C and Venter, JC and Smith, HO and Glass, JI and Hutchison, CA}, title = {Cloning whole bacterial genomes in yeast.}, journal = {Nucleic acids research}, volume = {38}, number = {8}, pages = {2558-2569}, doi = {10.1093/nar/gkq119}, pmid = {20211840}, issn = {1362-4962}, mesh = {Base Sequence ; Cloning, Molecular/*methods ; Diploidy ; Genetic Vectors/chemistry ; *Genome, Bacterial ; Molecular Sequence Data ; Mycoplasma/*genetics ; Mycoplasma genitalium/genetics ; Mycoplasma mycoides/genetics ; Mycoplasma pneumoniae/genetics ; Recombination, Genetic ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Most microbes have not been cultured, and many of those that are cultivatable are difficult, dangerous or expensive to propagate or are genetically intractable. Routine cloning of large genome fractions or whole genomes from these organisms would significantly enhance their discovery and genetic and functional characterization. Here we report the cloning of whole bacterial genomes in the yeast Saccharomyces cerevisiae as single-DNA molecules. We cloned the genomes of Mycoplasma genitalium (0.6 Mb), M. pneumoniae (0.8 Mb) and M. mycoides subspecies capri (1.1 Mb) as yeast circular centromeric plasmids. These genomes appear to be stably maintained in a host that has efficient, well-established methods for DNA manipulation.}, }
@article {pmid21626818, year = {2010}, author = {Doronin, BM and Denisova, OA}, title = {[Disturbances of lipid metabolism in the period of age androgen deficit in middle-aged and elderly men with ischemic stroke].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {110}, number = {12 Pt 2}, pages = {52-54}, pmid = {21626818}, issn = {1997-7298}, mesh = {Aged ; Androgens/blood/deficiency ; Cholesterol/blood ; Humans ; Hyperlipidemias/*blood ; Intracranial Arteriosclerosis/*blood/*epidemiology ; Lipoproteins, LDL/blood ; Male ; Middle Aged ; Stroke/*blood ; Testosterone/blood/*deficiency ; Triglycerides/blood ; }, abstract = {Blood concentrations of total cholesterol, beta-lipoproteins, triglycerides and testosterone were studied in 73 men (mean age 65.9 +/- 8.6 years) with acute ischemic stroke. The concentrations of testosterone and triglycerides in men decrease with age and those of cholesterol and beta-lipoproteins do not depend on the age. In middle-aged patients, the negative correlations were found between concentrations of testosterone and beta-lipoproteins (r = -0.404; p < 0.05); testosterone and cholesterol (r = -0.273; p < 0.001). In elderly patients, there were negative correlations between concentrations of testosterone and triglycerides (r = -0.348; p < 0.05). In middle-aged and elderly patients, concentrations of triglycerides and testosterone were negatively correlated (r = -0.478; p < 0.001). The lower blood testosterone level was associated with the higher risk of the development of atherosclerotic lesions of major arteries that allowed to estimate risks of ischemic stroke in middle-aged and elderly men.}, }
@article {pmid19882902, year = {2009}, author = {Baranova, EN and Sharipova, IN and Denisova, NM and Susekina, ME and Puzyrev, VF and Sarkisian, KA and Vorob'eva, MS and Burkov, AN and Ulanova, TI}, title = {[The capacities of current test systems to verify early HIV infection].}, journal = {Voprosy virusologii}, volume = {54}, number = {5}, pages = {37-40}, pmid = {19882902}, issn = {0507-4088}, mesh = {AIDS Serodiagnosis/*methods ; HIV Antibodies/blood ; HIV Core Protein p24/blood ; HIV Infections/blood/*diagnosis ; HIV-1/*immunology ; HIV-2/*immunology ; Humans ; Immunoblotting ; Immunoenzyme Techniques/*methods ; *Reagent Kits, Diagnostic ; Sensitivity and Specificity ; }, abstract = {The purpose of the present investigation was to comparatively evaluate the performance characteristics of the test systems designed to verify the positive results of screening survey for HIV infection, such as the solid-phase immunoassay DS-EIA-HIV-AB/AG-SPECTR (Diagnosticheskiye Sistemy (Diagnostic Systems) Research-and-Production Association, Nizhni Novgorod) and tests based on immune blotting (IB). The investigation examined 15 seroconversion panels produced by ZeptoMetrix (USA) and BBI (USA). The use of the DS-EIA-HIV-AB/AG-SPECTR test system determined 88 of the 167 seroconversion panels as HIV positive. The IB-based tests revealed only 45 of the 167 samples as positive. Consequently, the application of the DS-EIA-HIV-AB/AG-SPECTR test system is more effective than the IB-based tests in early HIV infection.}, }
@article {pmid19795792, year = {2009}, author = {Zemlianskikh, NG and Denisova, ON}, title = {[Changes in erythrocyte membrane-cytoskeleton complex, induced by dimethyl sulfoxide, polyethylene glycol, and low temperature].}, journal = {Biofizika}, volume = {54}, number = {4}, pages = {693-703}, pmid = {19795792}, issn = {0006-3029}, mesh = {Animals ; Cryoprotective Agents/*chemistry/pharmacology ; Cytoskeleton/*chemistry/metabolism ; Dimethyl Sulfoxide/*chemistry/pharmacology ; Dogs ; Erythrocyte Membrane/*chemistry/metabolism ; Freezing ; Oxidation-Reduction/drug effects ; Polyethylene Glycols/*chemistry/pharmacology ; Surface-Active Agents/*chemistry/pharmacology ; }, abstract = {The effect of the cryoprotectants DMSO and PEG-1500 as well as freezing-thawing on the proteins of the canine erythrocyte membrane-cytoskeleton complex has been studied using the cross-linking reagent diamide. It was shown that the intensity of distortions in the protein network structure correlated to an increase in SH-group accessibility for the oxidation by this compound and accordingly, the enhancement of the formation of high-molecular-weight protein aggregates. The maximum level of diamide-induced aggregability was revealed upon freezing of erythrocytes in liquid nitrogen without the cryoprotectant. The electrophoretical analysis of the ghost proteins of erythrocytes incubated with cryoprotectants showed a significant increase in the aggregation level only in cells present in the polymer solution. After the freezing-thawing cycle, the diamide-induced protein aggregability in erythrocytes cryopreserved with PEG-1500 strongly increased, while if DMSO was used for cell protection, the level of aggregates was much less pronounced than in the control. One can suppose that the exocellular cryoprotectant PEG-1500, as distinct from the endocellular cryoprotectant DMSO, is unable to provide the preservation of the structure of the membrane-cytoskeleton protein complex at the acceptable level necessary for the maintenance of cell integrity after the return to the physiological conditions.}, }
@article {pmid19705797, year = {2009}, author = {Stotskaia, TV and Mravian, SR and Vishniakova, MV and Vashchenko, AV and Stepanova, EA and Denisova, LB and Grigor'eva, NM}, title = {[Kawasaki disease in an adult European].}, journal = {Klinicheskaia meditsina}, volume = {87}, number = {7}, pages = {63-66}, pmid = {19705797}, issn = {0023-2149}, mesh = {Adult ; European Continental Ancestry Group ; Humans ; Male ; Mucocutaneous Lymph Node Syndrome/*diagnosis/drug therapy ; }, abstract = {A case of Kawasaki disease is reported with manifestations of autoimmune vasculitis and predominant affection of coronary arteries. The relevant literature review describes major symptoms of this pathology and risk factors of its atypical forms. It is emphasized that rare occurrence of Kawasaki disease among non-mongoloid subjects should not make the general practitioner les suspicious of this condition.}, }
@article {pmid19696314, year = {2009}, author = {Lartigue, C and Vashee, S and Algire, MA and Chuang, RY and Benders, GA and Ma, L and Noskov, VN and Denisova, EA and Gibson, DG and Assad-Garcia, N and Alperovich, N and Thomas, DW and Merryman, C and Hutchison, CA and Smith, HO and Venter, JC and Glass, JI}, title = {Creating bacterial strains from genomes that have been cloned and engineered in yeast.}, journal = {Science (New York, N.Y.)}, volume = {325}, number = {5948}, pages = {1693-1696}, doi = {10.1126/science.1173759}, pmid = {19696314}, issn = {1095-9203}, mesh = {Centromere ; *Cloning, Molecular ; DNA Methylation ; DNA Restriction Enzymes/genetics/metabolism ; Deoxyribonucleases, Type III Site-Specific/genetics ; *Gene Transfer Techniques ; *Genetic Engineering ; *Genome, Bacterial ; Mycoplasma capricolum/*genetics ; Mycoplasma mycoides/*genetics/growth & development/isolation & purification ; Plasmids ; Saccharomyces cerevisiae/*genetics ; Sequence Analysis, DNA ; Sequence Deletion ; Transformation, Bacterial ; }, abstract = {We recently reported the chemical synthesis, assembly, and cloning of a bacterial genome in yeast. To produce a synthetic cell, the genome must be transferred from yeast to a receptive cytoplasm. Here we describe methods to accomplish this. We cloned a Mycoplasma mycoides genome as a yeast centromeric plasmid and then transplanted it into Mycoplasma capricolum to produce a viable M. mycoides cell. While in yeast, the genome was altered by using yeast genetic systems and then transplanted to produce a new strain of M. mycoides. These methods allow the construction of strains that could not be produced with genetic tools available for this bacterium.}, }
@article {pmid19566074, year = {2009}, author = {Denisova, EA and Kirichenko, LL and Rushkevich, OP}, title = {[Structural and functional changes in heart under medical therapy in mental workers having arterial hypertension].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {5}, pages = {23-26}, pmid = {19566074}, issn = {1026-9428}, mesh = {Antihypertensive Agents/*therapeutic use ; Disease Progression ; Echocardiography ; Electrocardiography ; Female ; Follow-Up Studies ; Heart Ventricles/*diagnostic imaging/physiopathology ; Humans ; Hypertension/*drug therapy/etiology/physiopathology ; Male ; Middle Aged ; Occupational Diseases/*drug therapy/etiology/physiopathology ; Prognosis ; Stress, Psychological/*complications/physiopathology ; Ventricular Function, Left/*physiology ; }, abstract = {Aim of the study was to study main structural and functional parameters of heart, evaluate efficiency of treatment (Egiloc, Cardilopin, their combination) in arterial hypertension patients. Examinations including ECG, EchoCG were performed initially, in 3 and 6 months after the treatment start. The study covered 126 patients with arterial hypertension II degree, who received the medium-dose therapy, and 34 apparently healthy individuals.}, }
@article {pmid19537091, year = {2009}, author = {Lideman, LF and Denisov, DA and Gibadulin, RA and Denisova, GF}, title = {[Autoimmune response in HIV-infected patients is directed against CD4 domain 4].}, journal = {Voprosy virusologii}, volume = {54}, number = {3}, pages = {12-16}, pmid = {19537091}, issn = {0507-4088}, mesh = {Alanine/genetics ; Algorithms ; Amino Acid Sequence ; Amino Acid Substitution ; *Autoimmunity ; CD4 Antigens/chemistry/genetics/*immunology ; Cell Line ; Epitope Mapping ; Epitopes, T-Lymphocyte/chemistry/genetics/*immunology ; HIV Infections/*immunology ; HIV-1/*immunology ; Humans ; Models, Molecular ; Peptide Library ; Protein Structure, Tertiary/genetics ; }, abstract = {Phage display epitope library technology and a novel computer algorithm have been used for the localization of CD4 epitopes specific for monoclonal antibody (mAb) T6 and autoimmune antibodies found in an HIV infected patient. Both predicted epitope clusters have been shown to overlap and to be localized within the domain 4 of CD4. They included Cys303, Glu304, Glu330, and Lys331 amino acids. Few amino acids predicted by the algorithm as the epitope residues and two residues that did not relate to the epitope were sequentially substituted for Ala. Further analysis of the mutated forms of sCD4 expressed in 293T cells transfected with the corresponding DNAs, supported the predicted localization of the mAb T6 epitope. The results demonstrate that the autoimmune response in HIV-infected patients is directed against domain D4 of sCD4.}, }
@article {pmid19526099, year = {2008}, author = {Cheknyov, SB and Babayants, AA and Denisova, EA}, title = {Induction of interferon production by conformation-modified proteins of plasma gamma-globulin fraction.}, journal = {Bulletin of experimental biology and medicine}, volume = {146}, number = {5}, pages = {591-595}, pmid = {19526099}, issn = {0007-4888}, mesh = {Cells, Cultured ; Copper/metabolism ; Gene Expression Regulation/*drug effects ; Humans ; Interferon-gamma/metabolism ; Interferons/*metabolism ; Leukocytes/*drug effects/*secretion ; Protein Binding ; Protein Conformation ; Zinc/metabolism ; gamma-Globulins/*chemistry/metabolism/*pharmacology ; }, abstract = {Plasma gamma-globulin fraction proteins, copper and zinc cations, and metal-modified gamma-globulins induce the production of IFN by human leukocytes. Binding of zinc cations attenuates the realization of the IFN-inducing effects of human serum gamma-globulin, while binding of copper cations potentiated this effect. Activity of IFN and the dynamics of its production correspond to those in response to phytohemagglutinin stimulation. The pool of induced IFN contains acid-labile (up to 60%) and acid-stable (up to 40%) constituents. Anti-IFN-alpha antibodies do not modify activity of produced IFN. The results indicate the possibility of gamma-globulin conformation allowing stimulation or attenuation of the protein capacity to induce the production of IFN pool with predominant content of IFN-gamma.}, }
@article {pmid19518411, year = {2009}, author = {Denisov, SI and Lyutyy, TV and Denisova, ES and Hänggi, P and Kantz, H}, title = {Directed transport in periodically rocked random sawtooth potentials.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {79}, number = {5 Pt 1}, pages = {051102}, doi = {10.1103/PhysRevE.79.051102}, pmid = {19518411}, issn = {1539-3755}, abstract = {We study directed transport of overdamped particles in a periodically rocked random sawtooth potential. Two transport regimes can be identified which are characterized by a nonzero value of the average velocity of particles and a zero value, respectively. The properties of directed transport in these regimes are investigated both analytically and numerically in terms of a random sawtooth potential and a periodically varying driving force. Precise conditions for the occurrence of transition between these two transport regimes are derived and analyzed in detail.}, }
@article {pmid19514440, year = {2009}, author = {Denisova, EN and Sharipova, VR and Purlo, NV and Sukhanova, GA and Biriukova, LS}, title = {[Use of fractional plasma separation and adsorption (Prometheus technology) in the treatment of acute liver failure].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {2}, pages = {45-49}, pmid = {19514440}, issn = {0201-7563}, mesh = {Adolescent ; Adsorption ; Adult ; Aged ; Bilirubin/blood ; Extracorporeal Circulation/instrumentation/*methods ; Female ; Humans ; Liver Failure, Acute/blood/etiology/*therapy ; Male ; Middle Aged ; *Plasma ; Sorption Detoxification/instrumentation/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {This paper presents the results of treating 8 patients with acute liver failure, by using the separation and adsorption of fractional plasma (Prometheus technology). Twenty-five procedures lasting 5-6 hours were performed. Anticoagulation with heparin was made under guidance of coagulogram parameters. The results of testing blood parameters before and after a procedure and hemodynamic parameters are given. The investigations have demonstrated the effectiveness and safety of the procedure.}, }
@article {pmid19390580, year = {2009}, author = {Denisova, G and Denisov, D and Evelegh, C and Weissgram, M and Beck, J and Foley, SR and Bramson, JL}, title = {Characterizing complex polysera produced by antigen-specific immunization through the use of affinity-selected mimotopes.}, journal = {PloS one}, volume = {4}, number = {4}, pages = {e5309}, doi = {10.1371/journal.pone.0005309}, pmid = {19390580}, issn = {1932-6203}, mesh = {Algorithms ; Animals ; Cell Proliferation ; Epitopes/*chemistry/*immunology ; Immune Sera/*immunology ; Immunization ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Peptide Library ; Rats ; Receptor, ErbB-2/metabolism ; }, abstract = {BACKGROUND: Antigen-based (as opposed to whole organism) vaccines are actively being pursued for numerous indications. Even though different formulations may produce similar levels of total antigen-specific antibody, the composition of the antibody response can be quite distinct resulting in different levels of therapeutic activity.

Using plasmid-based immunization against the proto-oncogene HER-2 as a model, we have demonstrated that affinity-selected epitope mimetics (mimotopes) can provide a defined signature of a polyclonal antibody response. Further, using novel computer algorithms that we have developed, these mimotopes can be used to predict epitope targets.

METHODS: Special flat-parallel specimens and whole extracted teeth with restorations were scanned using a high-frequency (50 MHz) focused ultrasonic transducer. Visual acoustic images (B- and C-scans) of the cement-dentin interface were obtained nondestructively, analyzed and compared with optical images taken after the samples were cut along the scanning axis. The shear bonding strength of a subsection of specimens was tested in a Lloyd material testing machine.

RESULTS: An essential distinction between the acoustical properties associated with good and failed bonding has been shown. In the case of failed adhesion, the ultrasound signal reflection from the cement-dentin interface is up to four to seven times higher in magnitude than in the case of good bonding. The comparison of the ultrasound imaging data with the data obtained using an optical microscope revealed a strong correspondence with the acoustical and optical results with respect to the presence, position and dimensions of the defects. The specimens showing higher ultrasound reflection from cement/dentin interface have also shown lower shear bonding strength.

METHODS: Random samples of men and women aged 45-69 years were taken from population registers in Novosibirsk (Russia), Krakow (Poland) and six towns of the Czech Republic, recruiting nearly 29,000 people. Participants completed a questionnaire that included questions regarding their mother's and father's education (not available in the Czech Republic) and ownership of several household items when they were 10 years old. Participants' standing and sitting heights were measured and from these an estimate of leg length was derived. Associations between indicators of childhood socioeconomic circumstances and anthropometric measures were analysed using linear regression.

RESULTS: Russian individuals were shorter and reported fewer household assets at the age of 10 years than Czech and Polish individuals. Parental education and household assets were strongly associated with each other and both were independently associated with height, leg length and trunk length. Height was associated with childhood circumstances more strongly than leg length. The associations of childhood circumstances with the leg/trunk ratio were weak and inconsistent.

METHODS: Four cross-sectional surveys of school children aged 14-17 years in 1989 (n=656), in 1994 (n=620), in 1999 (n=626) and in 2003 (n=667) were carried out. Total sample was 2569 (1214 males and 1355 females). Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) were measured by enzymatic methods. LDL-C was calculated with Friedwald's formula. Associations of blood lipids with age, sex, year of study, body mass index (kg/m2), blood pressure and main nutrients of diet were measured by GLM method. Prevalence of dyslipidemia was evaluated with NCEP-peds criteria. Diet was estimated using 24-hour dietary recall.

RESULTS: During the 15-year period (1989-2003) mean serum TC decreased from 175 to 162 mg/dl in males and from 191 to 175 mg/dl in females (p < 0.001). Average levels of LDL-C also fell significantly during this period, but no changes in HDL-C levels were found. Females had significantly higher mean TC and LDL-C than did males at all surveys (p < 0.001). According to NCFP-peds criteria prevalence of high TC (200 mg/dl und more) during the period (1989-2003) significantly decreased from 22% to 8% (p < 0.01) in males and from 32% to 17% (p < 0.05) in females. Frequencies of low HDL-C (< 40 mg/dl) also decreased in boys and girls (p < 0.05 for both gender groups). Significant regression coefficients for TC controlled by age, sex and year of study were revealed with body mass index, diastolic blood pressure and triceps skinfolds. Trends in diet during the period showed significant decrease of total energy and basic nutrient intakes (proteins, fats and carbohydrates).

RESULTS: Prevalence of high TC, high LDL-C and low HDL-C significantly decreased in both gender groups. Prevalence of arterial hypertension also decreased in boys and girls. Frequency of overweight decreased more in girls. Trends in diet showed significant decreasing of total energy and basic nutrient intakes. Cigarette smoking rate decreased in boys and increased in girls. Physical inactivity rate was high in boys and girls.

CONCLUSION: Obtained data indicate similar trends to reduction in classical CVD risk factors, energy intake and life style changes among Siberian adolescents during the period of socioeconomic reforms in Russia.}, }
@article {pmid17924343, year = {2007}, author = {Derenko, M and Malyarchuk, B and Grzybowski, T and Denisova, G and Dambueva, I and Perkova, M and Dorzhu, C and Luzina, F and Lee, HK and Vanecek, T and Villems, R and Zakharov, I}, title = {Phylogeographic analysis of mitochondrial DNA in northern Asian populations.}, journal = {American journal of human genetics}, volume = {81}, number = {5}, pages = {1025-1041}, doi = {10.1086/522933}, pmid = {17924343}, issn = {0002-9297}, mesh = {Asia ; Asian Continental Ancestry Group/*genetics ; DNA, Mitochondrial/*genetics ; European Continental Ancestry Group/genetics ; Genetic Variation ; *Geography ; Haplotypes ; Humans ; Molecular Sequence Data ; *Phylogeny ; Principal Component Analysis ; Sequence Analysis, DNA ; }, abstract = {To elucidate the human colonization process of northern Asia and human dispersals to the Americas, a diverse subset of 71 mitochondrial DNA (mtDNA) lineages was chosen for complete genome sequencing from the collection of 1,432 control-region sequences sampled from 18 autochthonous populations of northern, central, eastern, and southwestern Asia. On the basis of complete mtDNA sequencing, we have revised the classification of haplogroups A, D2, G1, M7, and I; identified six new subhaplogroups (I4, N1e, G1c, M7d, M7e, and J1b2a); and fully characterized haplogroups N1a and G1b, which were previously described only by the first hypervariable segment (HVS1) sequencing and coding-region restriction-fragment-length polymorphism analysis. Our findings indicate that the southern Siberian mtDNA pool harbors several lineages associated with the Late Upper Paleolithic and/or early Neolithic dispersals from both eastern Asia and southwestern Asia/southern Caucasus. Moreover, the phylogeography of the D2 lineages suggests that southern Siberia is likely to be a geographical source for the last postglacial maximum spread of this subhaplogroup to northern Siberia and that the expansion of the D2b branch occurred in Beringia ~7,000 years ago. In general, a detailed analysis of mtDNA gene pools of northern Asians provides the additional evidence to rule out the existence of a northern Asian route for the initial human colonization of Asia.}, }
@article {pmid17886373, year = {2007}, author = {Mats, AN and Znamenskaia, LF and Fattiakhetdinova, ZA and Iashin, MM and Denisova, EV and Trofimova, IB}, title = {[Affinoleukin in combined treatment of psoriasis].}, journal = {Zhurnal mikrobiologii, epidemiologii, i immunobiologii}, volume = {}, number = {4}, pages = {32-38}, pmid = {17886373}, issn = {0372-9311}, mesh = {Adolescent ; Adult ; Aged ; Anti-Inflammatory Agents/therapeutic use ; Biological Products/administration & dosage/chemistry/*therapeutic use ; Cell Count ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; Injections, Subcutaneous ; Killer Cells, Natural/immunology ; Leukocytes/chemistry ; Male ; Membrane Proteins/administration & dosage/chemistry/isolation & purification/therapeutic use ; Middle Aged ; Molecular Weight ; Monocytes/cytology ; Psoriasis/blood/*drug therapy ; Receptors, Antigen, T-Cell, gamma-delta ; T-Lymphocyte Subsets/immunology ; Treatment Outcome ; }, abstract = {Open randomized controlled clinical trials in which 161 patients were included showed that Affinoleukin (commercial drug which contains low molecular weight proteins obtained from extract of human leukocytes membranes) was effective in treatment of psoriasis. Affinoleukin, when added to regular treatment, accelerated the establishment of remission and its duration by restoration of impaired regulatory and defensive functions of T-lymphocytes, particularly, gamma deltaT- and NKT-cells as well as monocytes and NK-cells. Regular treatment led to marked positive effect in 45% of patients with severe psoriasis and psoriasis of intermediate severity. Addition of Affinoleukin in combined treatment increased proportion of patients with marked positive effect to 72%. Magnitude of Affinoleukin effect was directly related with its dose and severity of psoriasis. Course of Affinoleukin injections (up to 30 units in adults) is worthwhile to use as immunobiological component of combined treatment of exacerbations of severe psoriasis and psoriasis of intermediate severity.}, }
@article {pmid17867504, year = {2007}, author = {Denisova, TV and Kazeev, KSh}, title = {[The influence of variable and constant magnetic fields on biota and biological activity of ordinary chernozem soils].}, journal = {Radiatsionnaia biologiia, radioecologiia}, volume = {47}, number = {3}, pages = {345-348}, pmid = {17867504}, issn = {0869-8031}, mesh = {Electromagnetic Fields/*adverse effects ; Radiation Monitoring/*methods ; Russia ; *Soil/analysis/standards ; *Soil Microbiology/standards ; }, abstract = {In model experiments on influence variable magnetic fields of industrial frequency (50 Hz) an induction of 1500 and of 6000 mkTl and the constant magnetic field an induction of 6000 mkTl and of 15000 mkTl during 5 days of exposure on biological properties of chernozem ordinary is shown, that the soil microflora is more sensitive to magnetic fields, than enzymes activity. Bacteria are more sensitive, than microscopic mushrooms. Dehydrogenase it is steady against influence of all variants. Constant magnetic field by the induction of 15000 mkTl rendered practically identical authentic overwhelming influence on catalase and saccharase activity - on 51 and 47% accordingly.}, }
@article {pmid17706584, year = {2007}, author = {Denisova, OV and Chernov, AV and Koledachkina, TY and Matvienko, NI}, title = {A tag-based approach for high-throughput analysis of CCWGG methylation.}, journal = {Analytical biochemistry}, volume = {369}, number = {2}, pages = {154-160}, doi = {10.1016/j.ab.2007.06.048}, pmid = {17706584}, issn = {0003-2697}, mesh = {Animals ; Base Sequence ; *DNA Methylation ; DNA Primers/*genetics ; DNA-Cytosine Methylases/*genetics/metabolism ; Deoxyribonucleases, Type II Site-Specific/*genetics/metabolism ; Electrophoresis, Polyacrylamide Gel ; Genomics/*methods ; Humans ; Reproducibility of Results ; }, abstract = {Non-CpG methylation occurring in the context of CNG sequences is found in plants at a large number of genomic loci. However, there is still little information available about non-CpG methylation in mammals. Efficient methods that would allow detection of scarcely localized methylated sites in small quantities of DNA are required to elucidate the biological role of non-CpG methylation in both plants and animals. In this study, we tested a new whole genome approach to identify sites of CCWGG methylation (W is A or T), a particular case of CNG methylation, in genomic DNA. This technique is based on digestion of DNAs with methylation-sensitive restriction endonucleases EcoRII-C and AjnI. Short DNAs flanking methylated CCWGG sites (tags) are selectively purified and assembled in tandem arrays of up to nine tags. This allows high-throughput sequencing of tags, identification of flanking regions, and their exact positions in the genome. In this study, we tested specificity and efficiency of the approach.}, }
@article {pmid17703276, year = {2007}, author = {Derenko, M and Malyarchuk, B and Denisova, G and Wozniak, M and Grzybowski, T and Dambueva, I and Zakharov, I}, title = {Y-chromosome haplogroup N dispersals from south Siberia to Europe.}, journal = {Journal of human genetics}, volume = {52}, number = {9}, pages = {763-770}, doi = {10.1007/s10038-007-0179-5}, pmid = {17703276}, issn = {1434-5161}, mesh = {Chromosomes, Human, Y/*classification/*genetics ; Europe ; Genetic Variation ; *Genetics, Population ; *Haplotypes ; Humans ; Male ; Microsatellite Repeats ; Phylogeny ; Polymorphism, Single Nucleotide ; Siberia ; }, abstract = {In order to reconstruct the history of Y-chromosome haplogroup (hg) N dispersals in north Eurasia, we have analyzed the diversity of microsatellite (STR) loci within two major hg N clades, N2 and N3, in a total sample of 1,438 males from 17 ethnic groups, mainly of Siberian and Eastern European origin. Based on STR variance analysis we observed that hg N3a is more diverse in Eastern Europe than in south Siberia. However, analysis of median networks showed that there are two STR subclusters of hg N3a, N3a1 and N3a2, that are characterized by different genetic histories. Age calculation of STR variation within subcluster N3a1 indicated that its first expansion occurred in south Siberia [approximately 10,000 years (ky)] and then this subcluster spread into Eastern Europe where its age is around 8 ky ago. Meanwhile, younger subcluster N3a2 originated in south Siberia (probably in the Baikal region) approximately 4 ky ago. Median network and variance analyses of STR haplotypes suggest that south Siberian N3a2 haplotypes spread further into Volga-Ural region undergoing serial bottlenecks. In addition, median network analysis of STR data demonstrates that haplogroup N2-A is represented by two subclusters, showing recent expansion times. The data obtained allow us to suggest Siberian origin of haplogroups N3 and N2 that are currently widespread in some populations of Eastern Europe.}, }
@article {pmid17694818, year = {2006}, author = {Vasil'ev, AIu and Tsyganova, LA and Ol'khova, EB and Vykliuk, MV and Serova, NS and Denisova, RB}, title = {[Radiation diagnosis for tuberculous gonitis in children].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {37-40}, pmid = {17694818}, issn = {0042-4676}, mesh = {Adolescent ; Arthrography/*methods ; Child ; Child, Preschool ; Diagnosis, Differential ; Humans ; Infant ; *Knee Joint ; Male ; Reproducibility of Results ; Severity of Illness Index ; Tuberculosis, Osteoarticular/*diagnostic imaging ; Ultrasonography ; }, abstract = {Tuberculous knee joint lesion in children is the most common form of articular pathology. The high sociomedical significance of this disease in modern society is determined by not only its prevalence, but also economic losses caused by high disability rates in children. The purpose of the study was to determine the possibilities and place of a comprehensive radiation study in the diagnosis of tuberculous gonitis in children. Sixty patients aged 10 months to 18 years were examined. Clinical studies were comprehensively assessed, by taking into account the collected history data and orhthopedic and laboratory findings. Surgery was made in 26 children. All the patients underwent mutiprojection X-ray study, knee joint ultrasound study being made in 48 patients. Knee joint X-ray study was performed on Siregraph (Siemens) apparatuses. Real-time ultrasonography was conducted on Aloka SSD-1100 and Aloka--3500+ apparatuses, by employing a 7.5-MHz linear transducer. According to P.G. Kornev (1971), three phases were identified in the course of tuberculous gonitis. These included prearthritic (the development of primary ostitis); arthritic (articular cartilage destruction, followed by the development of secondary arthritis; and postarthritic (sequels of prior tuberculous osteomyelitis) phases. Analysis indicated that the use of the routine X-ray study in combination with ultrasound scanning in the diagnosis of tuberculous gonitis in children yielded more adequate information on tissue and knee joint structural changes and made it possible to define further policy treatment and to predict the outcomes of the disease.}, }
@article {pmid17677236, year = {2007}, author = {Denisov, SI and Kostur, M and Denisova, ES and Hänggi, P}, title = {Analytically solvable model of a driven system with quenched dichotomous disorder.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {75}, number = {6 Pt 1}, pages = {061123}, doi = {10.1103/PhysRevE.75.061123}, pmid = {17677236}, issn = {1539-3755}, abstract = {We perform a time-dependent study of the driven dynamics of overdamped particles that are placed in a one-dimensional, piecewise linear random potential. This setup of spatially quenched disorder then exerts a dichotomous varying random force on the particles. We derive the path integral representation of the resulting probability density function for the position of the particles and transform this quantity of interest into the form of a Fourier integral. In doing so, the evolution of the probability density can be investigated analytically for finite times. It is demonstrated that the probability density contains both a delta -singular contribution and a regular part. While the former part plays a dominant role at short times, the latter rules the behavior at large evolution times. The slow approach of the probability density to a limiting Gaussian form as time tends to infinity is elucidated in detail.}, }
@article {pmid17603677, year = {2006}, author = {Cheknev, SB and Babaeva, EE and Denisova, EA and Vorob'eva, UA and Mongush, EM}, title = {Preparation of specimens of human serum gamma-globulin modified by copper and zinc and its immunochemical characteristics.}, journal = {Bulletin of experimental biology and medicine}, volume = {142}, number = {6}, pages = {710-713}, pmid = {17603677}, issn = {0007-4888}, mesh = {Cations/chemistry ; Copper/*chemistry ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Protein Binding ; Protein Conformation ; Proteins/chemistry ; Spectrophotometry, Ultraviolet ; Ultrafiltration ; Zinc/*chemistry ; gamma-Globulins/*chemistry/*immunology ; }, abstract = {Specimens of human serum gamma-globulin modified by molar excess of copper and zinc cations were obtained by molecular ultrafiltration. Conformation characteristics of the protein were determined by UV spectrophotometry. Immunochemical study included radial immunodiffusion test and direct and sandwich enzyme-linked immunosorbent assay. After binding of copper and zinc, the gamma-globulin molecule underwent conformation changes modifying presentation of antigenic determinants on the globule surface and their availability for recognition by specific antibodies. The effects of copper were much more pronounced than those of zinc cations.}, }
@article {pmid17486763, year = {2007}, author = {Derenko, MV and Maliarchuk, BA and Wozniak, M and Denisova, GA and Dambueva, IK and Dorzhu, CM and Grzybowski, T and Zakharov, IA}, title = {[Distribution of the male lineages of Genghis Khan's descendants in northern Eurasian populations].}, journal = {Genetika}, volume = {43}, number = {3}, pages = {422-426}, pmid = {17486763}, issn = {0016-6758}, mesh = {Asian Continental Ancestry Group/*genetics ; Chromosomes, Human, Y/*genetics ; Ethnic Groups/*genetics ; Humans ; Male ; Microsatellite Repeats ; Mongolia/ethnology ; Siberia/ethnology ; }, abstract = {Data on the variation of 12 microsatellite loci of Y-chromosome haplogroup C3 were used to screen lineages included in the cluster of Genghis Khan's descendants in 18 northern Eurasian populations (Altaian Kazakhs, Altaians-Kizhi, Teleuts, Khakassians, Shorians, Tyvans, Todjins, Tofalars, Sojots, Buryats, Khamnigans, Evenks, Mongols, Kalmyks, Tajiks, Kurds, Persians, and Russians; the total sample size was 1437 people). The highest frequency of haplotypes from the cluster of the Genghis Khan's descendants was found in Mongols (34.8%). In Russia, this cluster was found in Altaian Kazakhs (8.3%), Altaians (3.4%), Buryats (2.3%), Tyvans (1.9%), and Kalmyks (1.7%).}, }
@article {pmid17405285, year = {2006}, author = {Denisova, TV}, title = {[Egineering psychology and ergonomics in aviation].}, journal = {Aviakosmicheskaia i ekologicheskaia meditsina = Aerospace and environmental medicine}, volume = {40}, number = {6}, pages = {59-63}, pmid = {17405285}, issn = {0233-528X}, mesh = {Aerospace Medicine/*trends ; *Aviation ; Ergonomics/*methods ; Humans ; Russia ; }, }
@article {pmid17402591, year = {2007}, author = {Bugaeva, LI and Denisova, TD and Spasov, AA}, title = {[Transplacental effects of bemithyl].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {70}, number = {1}, pages = {40-43}, pmid = {17402591}, issn = {0869-2092}, mesh = {Animals ; Antioxidants/metabolism/*pharmacology ; Behavior, Animal/drug effects ; Benzimidazoles/metabolism/*pharmacology ; Female ; Fetal Development/drug effects ; Fetus/*drug effects ; Placenta/*metabolism ; Pregnancy ; Rats ; Rats, Inbred Strains ; }, abstract = {The daily administration of bemithyl (20 mg/kg) from 6 th to 16 th day of pregnancy in female rats led to the decrease in fetal death after the implantation and increased fetal body weight. The treatment of pregnant rats also led to acceleration of the development of physical condition and sensomotor reflexes of progeny in the postnatal period.}, }
@article {pmid17195631, year = {2006}, author = {Denisova, LB and Vorontsova, SV and Iaurova, NV}, title = {[Potentialities of new radiation technologies (ultrasonography, computed tomography, magnetic resonance imaging) in the diagnosis of endocrine diseases].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {1}, pages = {29-43}, pmid = {17195631}, issn = {0042-4676}, mesh = {Diagnosis, Differential ; *Endocrine System Diseases/diagnostic imaging/pathology ; Humans ; Magnetic Resonance Imaging/*methods ; Reproducibility of Results ; Tomography, X-Ray/*methods ; Ultrasonography ; }, abstract = {In the paper providing the data available in the literature and many years' experience gained by the Department of the Moscow Regional Clinical Research Institute, the authors describe the potentialities of the currently available radiation techniques in the diagnosis of surgical endocrine diseases. The incidence of various organ dysfunctions is presented. The authors also consider the introscopic symptoms of various endocrinopathies and outline the common specific features of the ultrasound, computed tomographic, and magnetic resonance imaging pattern of individual masses (including adipose tissue cysts and tumors). Emphasis is laid on the leading role of ultrasonography (USG) in the diagnosis of thyroid and parathyroid diseases and on the priorities of computed tomography (CT) and magnetic resonance imaging (MRI) in visualIzing the abnormal thymus, mediastinally ectopic glands, and pituitary tumors. The capacities of each technique in the diagnosis of endocrine space lesions of the pancreas and adrenals are defined. The increase in the frequency of endocrine abnormalities accidentally identified at USG, CT, and MRI, which is noted in the paper, fosters the development of new trends in endocrinology and points to the need for screening surveys (particularly patients who live in poor environmental areas).}, }
@article {pmid17195527, year = {2006}, author = {Kulagin, AD and Lisukov, IA and Kriuchkova, IV and Sizikova, SA and Gilevich, AV and Denisova, VV and Filimonov, PN and Meniaeva, EV and Pronkina, NV and Kozhevnikov, VS and Chernykh, ER and Kozlov, VA}, title = {[Diagnosis and treatment of aquired aplastic anemia].}, journal = {Terapevticheskii arkhiv}, volume = {78}, number = {11}, pages = {48-54}, pmid = {17195527}, issn = {0040-3660}, mesh = {Anemia, Aplastic/*diagnosis/drug therapy/*therapy ; Antilymphocyte Serum/therapeutic use ; *Bone Marrow Transplantation ; Combined Modality Therapy ; Cyclosporine/therapeutic use ; Female ; Humans ; *Immunosuppression ; Immunosuppressive Agents ; Male ; Treatment Outcome ; }, abstract = {AIM: To analyse the results of diagnosis and treatment of patients with aquired aplastic anemia (AA) in one center.

MATERIAL AND METHODS: All AA patients, diagnosed and treated in one clinic in 1998-2005, were included in the trial. In severe and very severe AA (SAA/VSAA) the patients (n = 19) received combined immunosuppressive therapy (IST) with antithymocytic globulin (ATG) and cyclosporin A (CsA), in non-severe AA (NSAA) the patients (n = 9) were given monotherapy with CsA. Allogenic transplantation of bone marrow (alloTBM) was made in 4 young patients with SAA/VSAA.

RESULTS: The diagnosis of AA was established in 33 patients (19 males and 14 females): NSAA in 9, SAA in 19, VSAA in 5, idiopathic--in 26, posthepatic--in 5, associated with pregnancy--in 2 patients. Age median was 20 years (13-53). The clone of paroxysmal nocturnal hemoglobinuria (PNH) was identified in 7 of 33 patients (21%), antigen HLA-DRB1 *15 in 6 of 11 patients (55%). In median of 26-month follow-up 31 patients (94%) were alive. In IST, complete or partial remissions were obtained in 88% patients. Median of the interval to achievement of transfusion independence made up 2.5 months. All the patients after alloTBM are in complete remission, chronic extensive transplant against host reaction was observed in one case.

CONCLUSION: Introduction of updated protocols provides long-term survival of more than 80% AA patients. To optimize treatment outcomes, it is necessary to include newly diagnosed AA patients into ongoing multicenter studies.}, }
@article {pmid17181064, year = {2006}, author = {Babaeva, EE and Vorobyova, UA and Denisova, EA and Medvedeva, DA and Cheknev, SB}, title = {Binding of zinc cations to human serum gamma-globulin.}, journal = {Bulletin of experimental biology and medicine}, volume = {141}, number = {5}, pages = {602-605}, pmid = {17181064}, issn = {0007-4888}, mesh = {Cations/*metabolism ; Globins/chemistry/*metabolism ; Humans ; Phenanthrolines ; Protein Binding ; Protein Conformation ; Spectrophotometry, Ultraviolet ; Ultrafiltration ; Zinc/analysis/*metabolism ; }, abstract = {Binding of zinc cations to human serum gamma-globulin was studied by molecular ultrafiltration. The content of free metal in the filtrate was evaluated by reaction with o-phenanthroline. Conformation characteristics of the protein were determined by UV spectrophotometry. Our findings suggest that gamma-globulin molecule contains several zinc binding sites differing by corresponding constants and successively occupied with increase in the content of bound metal. The parameters of zinc binding correspond to those obtained in experiments with copper. Conformation status of protein with bound zinc differs significantly from that of protein with bound copper cations.}, }
@article {pmid17114825, year = {2007}, author = {Paley, EL and Denisova, G and Sokolova, O and Posternak, N and Wang, X and Brownell, AL}, title = {Tryptamine induces tryptophanyl-tRNA synthetase-mediated neurodegeneration with neurofibrillary tangles in human cell and mouse models.}, journal = {Neuromolecular medicine}, volume = {9}, number = {1}, pages = {55-82}, pmid = {17114825}, issn = {1559-1174}, support = {EB01850/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/drug effects ; Brain/drug effects/metabolism/*pathology ; Cell Count ; Cell Line, Tumor ; Glucose/metabolism ; Hippocampus/metabolism/pathology ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Motor Activity/drug effects ; Neurodegenerative Diseases/metabolism/*pathology/psychology ; Neurofibrillary Tangles/*pathology ; Neuroglia/pathology ; Neurons/pathology ; Tryptamines/pharmacology/*physiology ; Tryptophan-tRNA Ligase/antagonists & inhibitors/*physiology ; }, abstract = {The neuropathological hallmarks of Alzheimer's disease (AD) and other taupathies include neurofibrillary tangles and plaques. Despite the fact that only 2-10% of AD cases are associated with genetic mutations, no nontransgenic or metabolic models have been generated to date. The findings of tryptophanyl-tRNA synthetase (TrpRS) in plaques of the AD brain were reported recently by the authors. Here it is shown that expression of cytoplasmic-TrpRS is inversely correlated with neurofibrillary degeneration, whereas a nonionic detergent-insoluble presumably aggregated TrpRS is simultaneously accumulated in human cells treated by tryptamine, a metabolic tryptophan analog that acts as a competitive inhibitor of TrpRS. TrpRSN- terminal peptide self-assembles in double-helical fibrils in vitro. Herein, tryptamine causes neuropathy characterized by motor and behavioral deficits, hippocampal neuronal loss, neurofibrillary tangles, amyloidosis, and glucose decrease in mice. Tryptamine induced the formation of helical fibrillary tangles in both hippocampal neurons and glia. Taken together with the authors' previous findings of tryptamine-induced nephrotoxicity and filamentous tangle formation in kidney cells, the authors' data indicates a general role of tryptamine in cell degeneration and loss. It is concluded that tryptamine as a component of a normal diet can induce neurodegeneration at the concentrations, which might be consumed along with food. Tryptophan-dependent tRNAtrp aminoacylation catalyzed by TrpRS can be inhibited by its substrate tryptophan at physiological concentrations was demonstrated. These findings indicate that the dietary supplementation with tryptophan as a tryptamine competitor may not counteract the deleterious influence of tryptamine. The pivotal role of TrpRS in protecting against neurodegeneration is suggested, providing an insight into the pathogenesis and a possible treatment of neurodegenerative diseases.}, }
@article {pmid17076067, year = {2006}, author = {Denisova, K and Singh, M and Kowler, E}, title = {The role of part structure in the perceptual localization of a shape.}, journal = {Perception}, volume = {35}, number = {8}, pages = {1073-1087}, doi = {10.1068/p5518}, pmid = {17076067}, issn = {0301-0066}, mesh = {Distance Perception/physiology ; Form Perception/*physiology ; Humans ; *Optical Illusions ; Psychometrics ; Psychophysics ; }, abstract = {The process of object localization may be accomplished with respect to a particular reference location, such as the center of gravity, COG (eg Vishwanath and Kowler, 2003 Vision Research 43 1637-1653). Here, we investigated how part structure affects an object's reference location. The reference location was evaluated with a measure of the illusory displacement of an internal target element embedded within a larger object (Morgan et al, 1990 Vision Research 30 1793-1810). To examine whether the reference location is different for shapes with part structure, two shapes were tested: circle (small and large; no part structure) and bell (shape with two parts, one larger than the other). Results were examined with respect to two predictions: either the location of an object is based on its shape as a whole, disregarding part structure (ie a single, overall COG), or the parts are processed separately (different COGs). With the circles, the results showed a systematic illusory displacement of the internal target toward the COG. With the bell, the illusion was significantly weaker than with both circles--even though the main part of the bell had the same size as the small circle, and its horizontal axis had the same extent as the large circle. Moreover, the distance judgments for the bell were consistent with a (weaker) reference point being located at the COG of the larger part, rather than at the COG of the entire bell. These results show that the part structure of a shape plays a role in the representation of its location, and that for complex shapes the perceived location of an embedded element depends more on the parts within which it is embedded, rather than on the whole shape.}, }
@article {pmid16881369, year = {2006}, author = {Denisova, LN}, title = {[Diet therapy of rheumatoid arthritis].}, journal = {Terapevticheskii arkhiv}, volume = {78}, number = {6}, pages = {84-88}, pmid = {16881369}, issn = {0040-3660}, mesh = {Arthritis, Rheumatoid/*diet therapy ; Humans ; }, }
@article {pmid16850925, year = {2006}, author = {Karal'nik, BV and Denisova, TG and Plazun, AA and Duĭsenova, RB}, title = {[Antigen-binding lymphocytes of tuberculin specificity in M. bovis-infected rabbits in the dynamics of treatment for tuberculosis].}, journal = {Problemy tuberkuleza i boleznei legkikh}, volume = {}, number = {5}, pages = {48-53}, pmid = {16850925}, issn = {1728-2993}, mesh = {Animals ; Antigen Presentation ; Mycobacterium bovis/*immunology ; Rabbits ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/*immunology ; Tuberculin/*immunology ; Tuberculosis/*immunology/*therapy ; }, abstract = {In M. bovis-infected rabbits, antigen-binding lymphocytes (ABL) of tuberculin specificity were detected within 7-105 days after inoculation. Due to etiotropic chemotherapy, ABL disappeared 31-45 days following inoculation. At the trial's end, the seeding rate and morphological changes in the organs of M. bovis-infected correlated with the content of ABL 105 days after inoculation. The early disappearance of ABL in the rats is regarded as an index of the efficiency of treatment for tuberculosis.}, }
@article {pmid16637277, year = {2006}, author = {Rechkina, EA and Denisova, GF and Masalova, OV and Lideman, LF and Denisov, DA and Lesnova, EI and Ataullakhanov, RI and Gur'ianova, SV and Kushch, AA}, title = {[Epitope mapping of antigenic determinants of hepatitis C virus proteins by phage display].}, journal = {Molekuliarnaia biologiia}, volume = {40}, number = {2}, pages = {357-368}, pmid = {16637277}, issn = {0026-8984}, mesh = {Amino Acid Sequence ; Animals ; Antibodies, Viral/*analysis/immunology ; *Epitope Mapping/methods ; Epitopes/*chemistry/genetics/immunology ; Female ; Hepacivirus/*chemistry/genetics/immunology ; Humans ; Mice ; Molecular Sequence Data ; *Peptide Library ; Protein Structure, Secondary/genetics ; Protein Structure, Tertiary/genetics ; RNA Helicases/chemistry/genetics/immunology ; Serine Endopeptidases/chemistry/genetics/immunology ; Viral Nonstructural Proteins/*chemistry/genetics/immunology ; }, abstract = {Study of individual hepatitis C (HCV) proteins could help to find a molecular structure and conformation, localization of antigenic and immunogenic determinants, to reveal of protective epitopes. It is necessary for practical medicine - development of diagnostic test-systems, vaccines and therapeutics. Linear and conformation dependent epitopes of HCV proteins was localized in this work and immunogenic properties of phage displayed peptides screened on monoclonal antibodies to HCV proteins have been investigated. Eleven epitopes of four HCV proteins have been studied. Three epitopes was found as linear, two epitopes were dependent on secondary structure of proteins and one epitope was dependent on tertiary structure of NS3 protein. Aminoacid sequences of other determinants have been determined and the distinct localization of these determinants will be continued after discovering of tertiary structure of HCV proteins. It was shown, that phage mimotope 3f4 is immunogenic and could induce specific hu- moral immune response to NS5A HCV protein. The data obtained could be useful for improving of HCV diagnostic test-systems, studying of amino acid substitutions and its influence on antigenic properties of the HCV proteins. The results could help to study an immune response in patients infected with different genotypes of HCV. Phage displayed peptides mimicking the antigenic epitopes of HCV proteins could be applied to development of HCV vaccine.}, }
@article {pmid16616781, year = {2007}, author = {Paley, EL and Smelyanski, L and Malinovskii, V and Subbarayan, PR and Berdichevsky, Y and Posternak, N and Gershoni, JM and Sokolova, O and Denisova, G}, title = {Mapping and molecular characterization of novel monoclonal antibodies to conformational epitopes on NH2 and COOH termini of mammalian tryptophanyl-tRNA synthetase reveal link of the epitopes to aggregation and Alzheimer's disease.}, journal = {Molecular immunology}, volume = {44}, number = {4}, pages = {541-557}, doi = {10.1016/j.molimm.2006.02.006}, pmid = {16616781}, issn = {0161-5890}, mesh = {Alzheimer Disease/immunology ; Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/chemistry/*immunology ; Antibody Specificity ; Cattle ; Cell Line, Tumor ; Cross Reactions ; Epitope Mapping ; *Epitopes/chemistry/genetics/immunology ; Humans ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Molecular Sequence Data ; Organ Specificity ; Protein Conformation ; Rabbits ; Species Specificity ; Tryptophan-tRNA Ligase/chemistry/*immunology ; }, abstract = {Tryptophanyl-tRNA synthetase (TrpRS) is an interferon-induced phosphoprotein with autoantigenic and cytokine activities detected in addition to its canonical function in tRNA aminoacylation. The availability of monoclonal antibodies (mAbs) specific for TrpRS is important for development of tools for TrpRS monitoring. A molecular characterization of two mAbs raised in mice, using purified, enzymatically active bovine TrpRS as the inoculating antigen, is presented in this report. These IgG1 antibodies are specific for bovine, human and rabbit but not E. coli TrpRS. Immunoreactivity and specificity of mAbs were verified with purified recombinant hTrpRS expressed in E. coli and TrpRS-derived synthetic peptides. One of the mAbs, 9D7 is able to disaggregate fibrils formed by Ser32-Tyr50 TrpRS-peptide. Epitope mapping revealed that disaggregation ability correlates with binding of 9D7 to this peptide in ELISA and immunocytochemistry. This epitope covers a significant part of N-terminal extension that suggested to be proteolytically deleted in vivo from the full-length TrpRS whereas remaining COOH-fragment possesses a cytokine activity. For epitope mapping of mAb 6C10, the affinity selected phage-displayed peptides were used as a database for prediction of conformational discontinuous epitopes within hTrpRS crystal structure. Using computer algorithm, this epitope is attributed to COOH-terminal residues Asp409-Met425. In immunoblotting, the 6C10 mAb reacts preferably with (i) oligomer than monomer, and (ii) bound than free TrpRS forms. The hTrpRS expression was shown to correlate with growth rates of neuroblastoma and pancreatic cancer cells. Immunohistochemically both mAbs revealed extracellular plaque-like aggregates in hippocampus of Alzheimer's disease brain.}, }
@article {pmid16579550, year = {2006}, author = {Denisova, TV and Kazeev, KSh}, title = {[The restoration of the enzyme activity of chernozem soil after gamma-irradiation].}, journal = {Radiatsionnaia biologiia, radioecologiia}, volume = {46}, number = {1}, pages = {89-93}, pmid = {16579550}, issn = {0869-8031}, mesh = {*Catalase/analysis/radiation effects ; *Gamma Rays ; Kinetics ; *Oxidoreductases/analysis/radiation effects ; Russia ; Soil/*analysis ; *beta-Fructofuranosidase/analysis/radiation effects ; }, abstract = {The Influence of gamma-radiation by dozes 1, 5, 10 and 20 kGy on enzyme activity of ordinary chemozem were studied. Dynamics of the restoration of the enzyme activity after the influence of gamma-radiation in model experiments in 3, 30, 90 and 180 days was investigated. The doze 1 kGy did no statistically significant influence on the investigated enzymes. Dehydrogenase is more radiosensitive enzyme than catalase. Values of the saccharase activity differed a significant variation so in most cases it has not been registered statistically significant changes. In 90-180 days of the incubation enzymes activity was restored up to control values. Dehydrogenase activity in 180 days in variants with dozes 10 and 20 kGy was restored up to a level of the control, over variants with dozes 1 and 5 kGy--is higher than the control over 78% and 23% accordingly. Saccharase activity in 180 days after the influence of gamma-radiation with a doze 20 kGy was on 61% lower than the control.}, }
@article {pmid16566435, year = {2006}, author = {Lebron, JA and Troilol, PJ and Pacchione, S and Griffiths, TG and Harper, LB and Mixson, LA and Jackson, BE and Michna, L and Barnum, AB and Denisova, L and Johnson, CN and Maurer, KL and Morgan-Hoffman, S and Niu, Z and Roden, DF and Wang, Z and Wolf, JJ and Hamilton, TR and Laux, KM and Soper, KA and Ledwith, BJ}, title = {Adaptation of the WHO guideline for residual DNA in parenteral vaccines produced on continuous cell lines to a limit for oral vaccines.}, journal = {Developments in biologicals}, volume = {123}, number = {}, pages = {35-44; discussion 55-73}, pmid = {16566435}, issn = {1424-6074}, mesh = {Administration, Oral ; Animals ; Cell Line ; Cercopithecus aethiops ; DNA/*administration & dosage/*adverse effects/pharmacokinetics ; Deoxyribonucleases ; Endocytosis ; Endosomes/physiology ; Female ; Humans ; Male ; Practice Guidelines as Topic ; Vaccines/administration & dosage/*standards ; Vero Cells ; World Health Organization ; }, abstract = {Although there is a WHO guidance for a limit on residual DNA for parenterally administered vaccines produced on continuous cell lines, there is no corresponding guidance for oral vaccines. To help determine an oral limit, we performed a study of Vero cell DNA uptake in rats, in which the relative uptake and persistence of Vero cell DNA administered orally was compared to its uptake when delivered intramuscularly (IM). The results of this study allowed the generation of an empirically derived IM versus oral factor (10(6)) representing the relative inefficiency of DNA uptake by oral administration. This factor was then applied to the WHO recommended parenteral limit of 10 ng/dose to determine a corresponding upper limit on the level of residual Vero cell DNA for an oral vaccine of 10 mg. As a conservative approach, this empirically determined limit was reduced 100-fold to 100 microg. Thus, the results of this animal study, together with additional evidence in the literature, support a residual DNA safety limit of 100 microg per dose for an oral vaccine produced on a continuous cell line.}, }
@article {pmid16297666, year = {2006}, author = {Grinshtein, N and Yang, TC and Parsons, R and Millar, J and Denisova, G and Dissanayake, D and Leitch, J and Wan, Y and Bramson, J}, title = {Recombinant adenovirus vaccines can successfully elicit CD8+ T cell immunity under conditions of extreme leukopenia.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {13}, number = {2}, pages = {270-279}, doi = {10.1016/j.ymthe.2005.09.018}, pmid = {16297666}, issn = {1525-0016}, mesh = {Adenoviridae/*genetics/*immunology ; Animals ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/*immunology/*pathology/virology ; Dendritic Cells/immunology ; Female ; Leukopenia/*immunology/pathology/*therapy ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Radiation Chimera ; Vaccines, Synthetic/administration & dosage/immunology ; Viral Vaccines/*administration & dosage/*immunology ; Whole-Body Irradiation ; }, abstract = {We have examined the efficacy of vaccination with recombinant adenovirus under conditions of extreme leukopenia in lethally irradiated mice reconstituted with autologous bone marrow. The expansion of antigen-specific CD8(+) T cells following immunization of lethally irradiated hosts paralleled the recovery of total CD8(+) T cells. Surprisingly, the numbers of antigen-specific CD8(+) T cells in lethally irradiated mice beyond 6 weeks postimmunization were comparable to the numbers found in nonirradiated controls. CD8(+) T cells elicited in the lethally irradiated hosts were functionally indistinguishable from those elicited in normal hosts. Antigen expression and presentation persisted for a longer period of time in the draining lymph nodes of irradiated mice compared to those of nonirradiated animals, suggesting that antigen presentation mechanisms were intact during the reconstitution period. Experiments employing allogeneic bone marrow demonstrated that radioresistant host antigen-presenting cells were responsible for antigen presentation during the process of immune reconstitution. These results demonstrate clear compatibility of adenovirus vaccines and cytotoxic therapy. Furthermore, these observations provide novel insights into the mechanisms of CD8(+) T cell activation following adenovirus immunization.}, }
@article {pmid16283003, year = {2005}, author = {Cheknev, SB and Babaeva, EE and Vorobeva, UA and Denisova, EA}, title = {Reactions between human serum gamma-globulin and zinc cations.}, journal = {Bulletin of experimental biology and medicine}, volume = {140}, number = {2}, pages = {209-212}, pmid = {16283003}, issn = {0007-4888}, mesh = {Cations ; Dose-Response Relationship, Drug ; Humans ; Hydrogen-Ion Concentration ; Protein Binding ; Protein Conformation ; Proteins/chemistry ; Spectrophotometry ; Time Factors ; Ultraviolet Rays ; Zinc/*chemistry ; gamma-Globulins/*chemistry ; }, abstract = {Interactions of human serum gamma-globulin with zinc cations in solution were studied by differential spectrophotometry in UV light. Supraphysiological concentrations of zinc caused an increment in optical density of protein solution reflecting the effect of gamma-globulin saturation with the metal. Zinc concentrations below physiological led to hypochromism in the protein absorption spectrum. Conformation changes in gamma-globulin during interactions with zinc are analyzed for the surface and intramolecular binding sites and are compared with the effects of copper cations.}, }
@article {pmid16273932, year = {2005}, author = {Denisova, OI and Klimenko, GIa}, title = {[Logbook system application in regional multi-field hospital].}, journal = {Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsiny}, volume = {}, number = {4}, pages = {38-41}, pmid = {16273932}, issn = {0869-866X}, mesh = {Hospital Information Systems ; Hospitals, General/*organization & administration ; Humans ; *Medical Records Systems, Computerized ; Organizational Innovation ; Russia ; }, }
@article {pmid16261343, year = {2006}, author = {Derenko, M and Malyarchuk, B and Denisova, GA and Wozniak, M and Dambueva, I and Dorzhu, C and Luzina, F and Miścicka-Sliwka, D and Zakharov, I}, title = {Contrasting patterns of Y-chromosome variation in South Siberian populations from Baikal and Altai-Sayan regions.}, journal = {Human genetics}, volume = {118}, number = {5}, pages = {591-604}, doi = {10.1007/s00439-005-0076-y}, pmid = {16261343}, issn = {0340-6717}, mesh = {*Chromosomes, Human, Y ; Ethnic Groups/*genetics ; *Genetics, Population ; Haplotypes ; Humans ; Male ; Siberia ; }, abstract = {In order to investigate the genetic history of autochthonous South Siberian populations and to estimate the contribution of distinct patrilineages to their gene pools, we have analyzed 17 Y-chromosomal binary markers (YAP, RPS4Y(711), SRY-8299, M89, M201, M52, M170, 12f2, M9, M20, 92R7, SRY-1532, DYS199, M173, M17, Tat, and LLY22 g) in a total sample of 1,358 males from 14 ethnic groups of Siberia (Altaians-Kizhi, Teleuts, Shors, Tuvinians, Todjins, Tofalars, Sojots, Khakassians, Buryats, Evenks), Central/Eastern Asia (Mongolians and Koreans) and Eastern Europe (Kalmyks and Russians). Based on both, the distribution pattern of Y-chromosomal haplogroups and results on AMOVA analysis we observed the statistically significant genetic differentiation between the populations of Baikal and Altai-Sayan regions. We suggest that these regional differences can be best explained by different contribution of Central/Eastern Asian and Eastern European paternal lineages into gene pools of modern South Siberians. The population of the Baikal region demonstrates the prevalence of Central/Eastern Asian lineages, whereas in the populations of Altai and Sayan regions the highest paternal contribution resulted from Eastern European descent is revealed. Yet, our data on Y-chromosome STRs variation demonstrate the clear differences between the South Siberian and Eastern European R1a1-lineages with the evolutionary ages compatible with divergence time between these two regional groups.}, }
@article {pmid16250592, year = {2005}, author = {Lideman, LF and Kasennova, EV and Denisova, GF and Stakhanova, VM and Zverev, SIa and Gibadulin, RA and Bobkov, AF}, title = {[Anti-CD4 autoimmunity in HIV-infected persons in Russia].}, journal = {Voprosy virusologii}, volume = {50}, number = {5}, pages = {15-19}, pmid = {16250592}, issn = {0507-4088}, mesh = {Amino Acid Sequence ; Autoantibodies/*blood ; CD4 Antigens/*immunology ; Consensus Sequence ; Epitopes, T-Lymphocyte ; Female ; Gene Products, nef/genetics ; HIV Infections/*blood/*virology ; HIV-1/*genetics ; Human Immunodeficiency Virus Proteins ; Humans ; Male ; Molecular Sequence Data ; Species Specificity ; Substance Abuse, Intravenous/blood ; Viral Regulatory and Accessory Proteins/genetics ; nef Gene Products, Human Immunodeficiency Virus ; }, abstract = {The frequency of anti-CD4 antibodies was determined in the sera or plasma derived from the patients infected with HIV-1 belonging to different genetic subgroups. The anti-CD4-antibodies in a dilution of > or = 1:1000 were found in 14% of the patients infected with the gagA/envA virus characteristic for injectable drug users in East Europe. The frequency of autoimmune antibodies among the HIV-infected patients with envB virus was substantially less (4.4%). Competitive ELISA using monoclonal antibodies to different CD4 domains demonstrated that irrespective of the viral genotype, the autoimmune epitope is located within the D4 or D3/D4 domains of CD4 receptor.}, }
@article {pmid16201340, year = {2005}, author = {Snetkova, EV and Levin, VM and Petroniuk, IuS and Denisov, AF and Bogachenkov, AN and Denisova, LA and Khramtsova, EA}, title = {[Application of the method of acoustic microscopy for the study of eye tissues].}, journal = {Morfologiia (Saint Petersburg, Russia)}, volume = {127}, number = {2}, pages = {72-75}, pmid = {16201340}, issn = {1026-3543}, mesh = {Animals ; Coturnix/anatomy & histology/embryology ; Embryo, Nonmammalian/anatomy & histology ; Eye/*anatomy & histology ; Goats/anatomy & histology ; Larva/anatomy & histology ; Microscopy, Acoustic/*methods ; Ranidae/anatomy & histology ; }, abstract = {The paper describes the results of evaluation of potentialities of the application of scanning acoustic microscopy, which is still relatively new and as yet uncommon method of biological research, for the supravital study of animal eye structure in species with different eyeball size. Using the eyes of a goat, quail embryo (in situ) and frog tadpole (in vivo) as the examples, it was shown that non-destructive nature of the method used allows for the study of peculiarities of major morphologic structures in the state that is close to the natural one. Some acoustic images are presented showing eye structural elements along with the results of quantitative characteristic of the cornea, sclera and iris.}, }
@article {pmid16078530, year = {2005}, author = {Igolkina, SN and Puzyrev, VF and Zinina, LG and Denisova, NM and Burkov, AN and Obriadina, AP and Ulanova, TI}, title = {[The enzyme immunological test systems "DS-EIA-HBeAg" and "DS-EIA-anti-HBe" for the specific diagnosis and prediction of the outcomes of acute and chronic hepatitis B].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {}, number = {6}, pages = {34-37}, pmid = {16078530}, issn = {0869-2084}, mesh = {Acute Disease ; Clinical Laboratory Techniques ; Enzyme-Linked Immunosorbent Assay/methods ; Hepatitis B/*diagnosis/physiopathology ; Hepatitis B e Antigens/*blood ; Hepatitis B, Chronic/*diagnosis/physiopathology ; Humans ; Predictive Value of Tests ; Prognosis ; }, }
@article {pmid16078433, year = {2005}, author = {Lashkevich, VA and Koroleva, GA and Lukashev, AN and Denisova, EV and Katargina, LA and Khoroshilova-Maslova, IP}, title = {[Acute enterovirus uveitis in infants].}, journal = {Voprosy virusologii}, volume = {50}, number = {3}, pages = {36-45}, pmid = {16078433}, issn = {0507-4088}, mesh = {Animals ; Antibodies, Viral/blood ; Antigens, Viral/immunology ; Cataract/etiology ; Cross Reactions ; Disease Models, Animal ; *Disease Outbreaks ; *Echovirus Infections/blood/complications/diagnosis/epidemiology ; Enterovirus B, Human/genetics/immunology ; Eye/virology ; Glaucoma/etiology ; Humans ; Infant ; Iris/pathology ; Molecular Epidemiology ; Neutralization Tests ; Phylogeny ; Primates ; Pupil Disorders ; RNA, Viral/genetics ; Russia/epidemiology ; *Uveitis/blood/complications/diagnosis/epidemiology ; Vision Disorders/etiology ; }, abstract = {Enterovirus uveitis (EU) is a new infant eye disease that was first detected and identified in Russia in 1980-1981. Three subtypes of human echoviruses (EV19K, EV11A, and EV11/B) caused 5 nosocomial outbreaks of EU in different Siberian cities and towns in 1980-1989, by affecting more than 750 children mainly below one year of age. Sporadic and focal EU cases (more than 200) were also retrospectively diagnosed in other regions of Russia and in different countries of the former Soviet Union. There were following clinical manifestations: common symptoms of the infection; acute uveitis (rapid focal iridic destruction, pupillary deformities, formation of membranes in the anterior chamber of the eye); and in 15-30% of cases severe complications, cataract, glaucoma, vision impairments. Uveitis strains EV19 and EV11 caused significant uveitis in primates after inoculation into the anterior chamber of the eye, as well as sepsis-like fatal disease with liver necrosis after venous infection. The uveitis strains are phylogenetically and pathogenetically close for primates to strains EV19 and EV11 isolated from young children with sepsis-like disease. The contents of this review have been published in the Reviews in Medical Virology, 2004, vol. 14, p. 241-254.}, }
@article {pmid16044839, year = {2005}, author = {Pogozheva, AV and Denisova, NN and Derbeneva, SA and Anykina, NV and Kondakova, NM}, title = {[Application of nutritional formulare in the dietotherapy in patients with cardiovascular diseases].}, journal = {Voprosy pitaniia}, volume = {74}, number = {3}, pages = {32-38}, pmid = {16044839}, issn = {0042-8833}, mesh = {Adult ; Aged ; Cardiovascular Diseases/*diet therapy ; *Enteral Nutrition ; Female ; *Food, Formulated ; Humans ; Lipid Metabolism ; Male ; Middle Aged ; Obesity/*diet therapy ; }, abstract = {It was found that the including of nutritional formulae in the dietary therapy for patients with cardiovascular diseases and obesity has been evaluated, had a positive effect on the clinical presentation of disease, lipid metabolism and the dynamic of body composition of patients.}, }
@article {pmid16034353, year = {2005}, author = {Garashchenko, TI and Denisova, OA and Kotov, RV}, title = {[Initial antibiotic therapy in acute otitis media and acute sinusitis in children].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {3}, pages = {62-63}, pmid = {16034353}, issn = {0042-4668}, mesh = {Acute Disease ; Administration, Oral ; Amoxicillin/administration & dosage/*therapeutic use ; Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Otitis Media, Suppurative/*drug therapy/*epidemiology/microbiology ; Sinusitis/*drug therapy/*epidemiology/microbiology ; Suspensions ; Treatment Outcome ; }, }
@article {pmid15974299, year = {2004}, author = {Malyarchuk, B and Derenko, M and Grzybowski, T and Lunkina, A and Czarny, J and Rychkov, S and Morozova, I and Denisova, G and Miścicka-Sliwka, D}, title = {Differentiation of mitochondrial DNA and Y chromosomes in Russian populations.}, journal = {Human biology}, volume = {76}, number = {6}, pages = {877-900}, pmid = {15974299}, issn = {0018-7143}, mesh = {Chromosomes, Human, Y/*genetics ; DNA, Mitochondrial/*genetics ; European Continental Ancestry Group/genetics ; Female ; Genetic Heterogeneity ; Genetic Variation ; *Genetics, Population ; Haplotypes ; Humans ; Male ; *Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Russia ; }, abstract = {The genetic composition of the Russian population was investigated by analyzing both mitochondrial DNA (mtDNA) and Y-chromosome loci polymorphisms that allow for the different components of a population gene pool to be studied, depending on the mode of DNA marker inheritance. mtDNA sequence variation was examined by using hypervariable segment I (HVSI) sequencing and restriction analysis of the haplogroup-specific sites in 325 individuals representing 5 Russian populations from the European part of Russia. The Y-chromosome variation was investigated in 338 individuals from 8 Russian populations (including 5 populations analyzed for mtDNA variation) using 12 binary markers. For both uniparental systems most of the observed haplogroups fell into major West Eurasian haplogroups (97.9% and 99.7% for mtDNA and Y-chromosome haplogroups, respectively). Multidimensional scaling analysis based on pairwise F(ST) values between mtDNA HVSI sequences in Russians compared to other European populations revealed a considerable heterogeneity of Russian populations; populations from the southern and western parts of Russia are separated from eastern and northern populations. Meanwhile, the multidimensional scaling analysis based on Y-chromosome haplogroup F(ST) values demonstrates that the Russian gene pool is close to central-eastern European populations, with a much higher similarity to the Baltic and Finno-Ugric male pools from northern European Russia. This discrepancy in the depth of penetration of mtDNA and Y-chromosome lineages characteristic for the most southwestern Russian populations into the east and north of eastern Europe appears to indicate that Russian colonization of the northeastern territories might have been accomplished mainly by males rather than by females.}, }
@article {pmid15938103, year = {2005}, author = {Biriukova, LS and Purlo, NV and Denisova, EN and Mondoev, LG and Levina, AA and Galstian, GM}, title = {[Use of continuous high-volume hemofiltration in patients with sepsis and multiple organ dysfunction].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {2}, pages = {69-71}, pmid = {15938103}, issn = {0201-7563}, mesh = {Adult ; Biomarkers/blood ; Cytokines/blood ; Enzymes/blood ; Female ; Hemofiltration/adverse effects/*methods ; Humans ; *Kidneys, Artificial ; Male ; Middle Aged ; Multiple Organ Failure/*therapy ; Online Systems ; Sepsis/*therapy ; }, abstract = {The paper gives the authors' experience in performing continuous high-volume hemofiltration in 38 patients with sepsis and multiple organ failure. The kinetics of proinflammatory cytokines and a number of plasma enzymes as markers of substances having a relatively high molecular mass was studied. The advantages of a procedure using an artificial kidney apparatus equipped with an on-line substituting fluid preparation system are described. The possibilities of correcting the parameters of homeostasis are the principles of maintenance of a hemostatic system in this group of patients during the procedure are presented. The drawbacks of this technique are also described.}, }
@article {pmid15934363, year = {2005}, author = {Spasov, AA and Bugaeva, LI and Denisova, TD and Smirnova, LA}, title = {[The effect of bemithyl on the onthogenesis of rats].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {68}, number = {2}, pages = {28-32}, pmid = {15934363}, issn = {0869-2092}, mesh = {Administration, Oral ; Animals ; Animals, Newborn ; Anticonvulsants/administration & dosage/*adverse effects ; Benzimidazoles/administration & dosage/*adverse effects ; Female ; *Lactation/drug effects ; Male ; Rats ; Sexual Maturation/*drug effects ; Time ; }, abstract = {Female rats were treated with bemithyl (20 and 100 mg/kg) via a gastric tube during a 16-day period of lactation. It was found that the drug is transferred with breast milk to the organism of newborns, which leads to nonuniformities in their development. Among the early effects of bemithyl, most pronounced is the stimulating action upon maturation (muscle strength) and the development of sensor-locomotor reflexes; in the spectrum of long-term effects, the drug influence upon pubescence processes was manifested.}, }
@article {pmid15921200, year = {2005}, author = {Denisova, NN and Baturin, AK and Pogozheva, AV}, title = {[Analysis by bioelectrical impedance of body composition of patients with cardiovascular diseases and obesity].}, journal = {Voprosy pitaniia}, volume = {74}, number = {2}, pages = {20-25}, pmid = {15921200}, issn = {0042-8833}, mesh = {Adult ; Aged ; *Body Composition ; *Body Mass Index ; Cardiovascular Diseases/complications/*physiopathology ; Electric Impedance ; Female ; Humans ; Male ; Middle Aged ; Obesity/complications/diet therapy/*physiopathology ; }, abstract = {Authors of article have recently analyzed the dynamic of body composition of patients with cardiovascular diseases and obesity by bioelectrical impedance analysis. It was found a difference of body composition in different groups of patients.}, }
@article {pmid15881156, year = {2005}, author = {Katargina, LA and Khvatova, AV and Kogoleva, LV and Denisova, EV}, title = {[Problems and outlooks for the preventive treatment of retinopathy in prematures].}, journal = {Vestnik oftalmologii}, volume = {121}, number = {2}, pages = {38-41}, pmid = {15881156}, issn = {0042-465X}, mesh = {Cryosurgery/*trends ; Disease Progression ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Laser Coagulation/*trends ; Refraction, Ocular/physiology ; Retina/pathology/surgery ; Retinopathy of Prematurity/pathology/physiopathology/*prevention & control ; Treatment Outcome ; }, abstract = {The immediate and remote (up to 7 years) results of preventive cryo- and/or lasercoagulation of avascular retinal zones made in 390 children with active progressing retinopathy of prematures (RP) were analyzed. The efficiency of cryocoagulation in processes localized in zones 2-3 of the eye bottom made 92%, and that of the combined technique (laser- and cryocoagulation) with lesions in zones 1-2 and with plus-diseases was up to 80%. The preventive treatment is indicated for the 3d threshold (ordinary clinical course) and before-threshold (with plus-disease and localization zone 1) stages. Such treatment is not justified when undertaken early and in developed retinal detachment. Further research of the disease pathogenesis is needed to enhance the efficiency of the RP treatment, i.e. research of growth factors of endothelial vessels, autoimmune reaction to S-antigen of the retina and of dosed oxygentherapy etc.}, }
@article {pmid15881151, year = {2005}, author = {Krichevskaia, GI and Andzhelov, VO and Katargina, LA and Starikova, AV and Denisova, EV and Zvonarev, AIu and Kuliakina, MN and Tsutskiridze, NG}, title = {[Reactivation of persistent herpes virus infection as a factor of endogenous uveitis in children].}, journal = {Vestnik oftalmologii}, volume = {121}, number = {2}, pages = {22-24}, pmid = {15881151}, issn = {0042-465X}, mesh = {Adolescent ; Antibodies, Viral/blood ; Child ; Child, Preschool ; Cytomegalovirus/growth & development/immunology ; Cytomegalovirus Infections/immunology/transmission/virology ; DNA, Viral/immunology ; Follow-Up Studies ; Herpes Simplex/immunology/transmission/*virology ; Herpesvirus 1, Human/*growth & development/immunology ; Humans ; Immunoenzyme Techniques ; Infant ; Infectious Disease Transmission, Vertical ; Lymphocytes/immunology ; Recurrence ; Severity of Illness Index ; Uveitis/blood/immunology/*virology ; }, abstract = {Two hundred and fifty-five children with endogenous uveitis, aged 2 months to 15 years, were examined. 73-93% of children were chronically infected by different viruses of the human herpes group; mycoplasmal past-infection was detected in only 13% of them and Chlamydia past-infection _ in 3.7% of them. Herpes simplex virus of type 1 reactivated reliably more often versus other types of Herpesviridae. Reactivation of cytomegalovirus infection prevailed in mothers who gave birth to children with intrauterine uveitis. A prolonged active replication of herpes virus was primarily observed in children with a Suppressed cell antiviral immunity component. Uveitis in such children was notable for a severe clinical course and trend towards often relapses.}, }
@article {pmid15881100, year = {2005}, author = {Denisova, TP and Shkoda, AS and Malinova, LI and Astaf'eva, NG}, title = {[Social stress as a risk factor for ischemic heart disease].}, journal = {Terapevticheskii arkhiv}, volume = {77}, number = {3}, pages = {52-55}, pmid = {15881100}, issn = {0040-3660}, mesh = {Humans ; Myocardial Infarction/*epidemiology/etiology ; Risk Factors ; Russia ; Socioeconomic Factors ; Stress, Psychological/*complications ; }, abstract = {AIM: To study dynamics of ischemic heart disease in exposure of the population of an industrial city to social-economic stress.

MATERIAL AND METHODS: Official annual records of Saratov city Health Administration for 1989-1998. In public health evaluation, cardiovascular morbidity is the index rapidly reacting to social-economic changes. Descrete data of myocardial infarction and angina prevalence for the analysed time were approximated by polynomes of high degree. As a result, the first and second derivatives--speed and acceleration--were obtained.

RESULTS: A rise in MI morbidity reflected a rise in social tension. The disturbance of the population system of an industrial center (in conditions of a social stress) is accompanied by marked deformation of the profile of cardiovascular diseases in the industrial region: the growth of MI prevalence is associated with lowering of angina pectoris morbidity.

CONCLUSION: A rise in MI incidence rate is proposed as an indicator of social-economic stability or instability. Instability of IHD morbidity in the population allows consideration of social stress as its risk factor.}, }
@article {pmid15869125, year = {2005}, author = {Denisova, NA and Booth, SL}, title = {Vitamin K and sphingolipid metabolism: evidence to date.}, journal = {Nutrition reviews}, volume = {63}, number = {4}, pages = {111-121}, pmid = {15869125}, issn = {0029-6643}, mesh = {Animals ; Brain/*metabolism ; Humans ; Sphingolipids/chemistry/*metabolism ; Vitamin K/*physiology ; }, abstract = {The brain is enriched with sphingolipids, which are important membrane constituents and major lipid signaling molecules that have a role in motor and cognitive behavior. Vitamin K has been implicated in brain sphingolipid metabolism for more than 30 years. The in vitro and in vivo studies to date suggest a role of vitamin K in the regulation of multiple enzymes involved in sphingolipid metabolism within the myelin-rich regions in the brain. However, the precise mechanisms of action are not well understood. Further, the physiological consequences of the observed effects of vitamin K on sphingolipid metabolism have not been systematically studied.}, }
@article {pmid15829299, year = {2005}, author = {Meyuhas, R and Noy, H and Montefiori, DC and Denisova, G and Gershoni, JM and Gross, G}, title = {HIV-1 neutralization by chimeric CD4-CG10 polypeptides fused to human IgG1.}, journal = {Molecular immunology}, volume = {42}, number = {9}, pages = {1099-1109}, doi = {10.1016/j.molimm.2004.11.002}, pmid = {15829299}, issn = {0161-5890}, mesh = {Antibodies, Monoclonal/*immunology ; CD4 Antigens/genetics/*immunology ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; Epitopes/immunology ; HIV Envelope Protein gp120/immunology ; HIV-1/*immunology ; Humans ; Immunoglobulin G/*immunology ; Immunoglobulin Variable Region/genetics/immunology ; Neutralization Tests ; Receptors, HIV/immunology ; Recombinant Fusion Proteins/immunology/isolation & purification ; Transfection ; }, abstract = {The envelope glycoprotein of HIV-1 is the principal target for entry inhibitors. The use of soluble CD4 has been found to be impractical as most clinical isolates are resistant to neutralization at feasible concentrations. CG10 is one of a small group of monoclonal antibodies specific to CD4-induced epitopes, which are structurally associated with the chemokine receptor-binding site and are capable of blocking the interaction of gp120 with its obligatory co-receptor. We have reasoned that fusing the single chain Fv of CG10 with CD4 can lead to increased HIV-1 neutralization activity and that this effect could be further enhanced by engrafting this chimeric construct onto an IgG Fc. Here we report the cloning of the genes encoding the variable regions of CG10 heavy and light chains and demonstrate that when attached to human IgG1 Fc, the single chain Fv of CG10 retains the binding properties of the original mouse antibody. Fusing CG10 single chain Fv with the gp120-binding portion of CD4 on a human IgG1 Fc backbone results in stronger binding of gp120 of different tropisms and in enhanced neutralization of laboratory-adapted strains and most, but not all, clade B and clade C isolates tested. Our findings underscore the potential use of CD4-based fusion proteins in the design of HIV immuno-therapeutics.}, }
@article {pmid15822641, year = {2005}, author = {Denisova, NN and Pogozheva, AV and Baturin, AK}, title = {[The nutrition analysis of the patients with cardio-vascular diseases].}, journal = {Voprosy pitaniia}, volume = {74}, number = {1}, pages = {24-27}, pmid = {15822641}, issn = {0042-8833}, mesh = {Adult ; Age Factors ; Cardiovascular Diseases/*diet therapy ; Eating ; Energy Intake ; Feeding Behavior ; Female ; Humans ; Hypertension/diet therapy ; Male ; Middle Aged ; Myocardial Ischemia/diet therapy ; *Nutrition Assessment ; Software ; }, abstract = {Authors of article have recently analyzed the actual food intake from patients with cardiovascular diseases with the help of a new computer program, based on frequency method. It was found a disbalance of intake main food components in different groups of patients.}, }
@article {pmid15751286, year = {2005}, author = {Denisova, EL and Gorshkov, AI and Liakhova, NP}, title = {[Influence of environmental factors on human health (in case of Orekhovo-Zuyevo)].}, journal = {Gigiena i sanitariia}, volume = {}, number = {1}, pages = {6-8}, pmid = {15751286}, issn = {0016-9900}, mesh = {Adolescent ; Adult ; Age Factors ; *Air Pollution ; Child ; *Health Status ; Humans ; Industry ; *Nutritional Physiological Phenomena ; Russia ; Surveys and Questionnaires ; Urban Population ; }, abstract = {The paper analyzes the actual nutrition in 301 schoolchildren (142 children and 159 adolescents), the state of ambient air and the health status of the population in 5 districts of the town of Orekhovo-Zuyevo. Non-balanced diets and ambient air pollution have been ascertained to negatively affect human health.}, }
@article {pmid15727143, year = {2004}, author = {Tsinberg, MB and Deriabin, DG and Denisova, IV}, title = {[Biological characterization of Bifidobacterium and Lactobacillus preparations made with the use of hydrolysate-milk and hydrolysate-soybean media].}, journal = {Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]}, volume = {49}, number = {8-9}, pages = {29-33}, pmid = {15727143}, issn = {0235-2990}, mesh = {Animals ; *Antibiosis ; *Bacterial Adhesion ; Bifidobacterium/growth & development/*physiology ; Culture Media ; Escherichia coli/physiology ; Hydrolysis ; Lactobacillus/growth & development/*physiology ; Milk ; *Probiotics ; Soybeans ; Staphylococcus aureus/physiology ; }, abstract = {A complex of biological characteristics important for design of the therapeutic and prophylactic activities of Bifidobacterium and Lactobacillus preparations made with the use of hydrolysate-milk and hydrolysate-soybean media was comparatively estimated. The use of the hydrolysate-soybean medium resulted in an increase of the antagonistic activity of the preparations against a number of opportunistic pathogens that was not connected with changing of their acidity and the content of lysozyme, a bacteriolytic enzyme in the culture fluid. The change in the cultivation conditions due to substitution of the hydrolysate-milk medium for the hydrolysate-soybean medium stimulated the adhesive capacity of the production strains used in the study, which was especially evident with respect to the representatives of the genus Bifidobacterium.}, }
@article {pmid15704443, year = {2004}, author = {Denisova, LB and Vorontsova, SV and Platonova, AG}, title = {[To the potentialities of computed tomographic diagnosis of renal lymphoma].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {39-44}, pmid = {15704443}, issn = {0042-4676}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Diagnosis, Differential ; Disease Progression ; Fatal Outcome ; Female ; Humans ; Kidney Neoplasms/*diagnostic imaging/drug therapy ; Lymphoma/*diagnostic imaging/drug therapy ; Middle Aged ; *Tomography, X-Ray Computed ; }, }
@article {pmid15704441, year = {2004}, author = {Denisova, LB and Vorontsova, SV and Eme'ianova, LN}, title = {[Role of new radiation techniques (ultrasonography, computed tomography, and magnetic resonance imaging) in the diagnosis of incidentally discovered adrenal masses].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {25-33}, pmid = {15704441}, issn = {0042-4676}, mesh = {Adrenal Gland Neoplasms/*diagnosis ; Adrenal Glands/*pathology ; Diagnosis, Differential ; Diagnostic Imaging/*methods ; Humans ; Magnetic Resonance Imaging ; Reproducibility of Results ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {The authors analyze the current views of incidentally discovered adrenal masses and the potentialities of ultrasound study (US), computed tomography (CT), and magnetic resonance imaging (MRI) in their detection and presents the US, CT, and MRI symptoms of different incidentally discovered adrenal masses. Due to the availability and almost extensive application of US apparatuses, they define the importance of US screening of the adrenal region and emphasize the capacities of echographic differentiation of cystic and solid adrenal masses in patients with different diseases of the abdomen and retroperitoneal space. The authors also note the basic role of CT and MRI in the specified topical diagnosis of retroperitoneal space lesions and in the presumption of the morphological structure of some tumor and tumoroid (hyperplasia-type) adrenal changes.}, }
@article {pmid15697655, year = {2005}, author = {Denisov, SI and Denisova, ES and Hänggi, P}, title = {Ratchet transport for a chain of interacting charged particles.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {71}, number = {1 Pt 2}, pages = {016104}, doi = {10.1103/PhysRevE.71.016104}, pmid = {15697655}, issn = {1539-3755}, abstract = {We study analytically and numerically the overdamped, deterministic dynamics of a chain of charged, interacting particles driven by a longitudinal alternating electric field and additionally interacting with a smooth ratchet potential. We derive the equations of motion, analyze the general properties of their solutions and find the drift criterion for chain motion. For ratchet potentials of the form of a double-sine and a phase-modulated sine it is demonstrated that both, a so-called integer and fractional transport of the chain, can occur. Explicit results for the directed chain transport for these two classes of ratchet potentials are presented.}, }
@article {pmid15689127, year = {2004}, author = {Supriaga, VG and Tsybina, TN and Denisova, TN and Morozov, EN and Romanenko, NA and Starkova, TV}, title = {[The first case of diagnosis of dirofilariasis from the microfilariae detected in the human subcutaneous tumor punctate].}, journal = {Meditsinskaia parazitologiia i parazitarnye bolezni}, volume = {}, number = {4}, pages = {6-8}, pmid = {15689127}, issn = {0025-8326}, mesh = {Animals ; Diagnosis, Differential ; Dirofilaria/*isolation & purification ; Dirofilariasis/*diagnosis/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Russia/epidemiology ; Soft Tissue Neoplasms/*diagnosis/parasitology ; Subcutaneous Tissue/parasitology ; Thorax ; }, abstract = {The paper describes the first case of diagnosis of dirofilariasis from the microfilariae detected in the subcutaneous tumor punctate from a person who has the clinical manifestations of D. repens invasion and resides in the Saratov Region that is endemic in dirofilariasis. The fact of detection of microfilariae in the man undergone invasion is assessed not only as the first case in the lifetime diagnosis of the first case of diagnosis of subcutaneous dirofilariasis, but also as the first case of verification of that a female can achieve sexual maturity in the organism of an accidental host and its impregnation if there are even single specimens of both sexes, which is characteristic in human invasiveness. On this basis, the authors consider it wrong to refer this helminthiasis to as a group of diseases defined as "Larva migrans cutaneous" since this is inconsistent with the biology of a causative agent that accomplishes migration at the adult stage in the host's organism and does not orient a physician to establish a correct clinical and parasitological diagnosis.}, }
@article {pmid15685857, year = {2004}, author = {Denisova, SN and Iukhtina, NV and Balabolkin, II and Korotkova, TN and Sentsova, TB and Belitskaia, MIu and Volkova, EA and Kon', IIa}, title = {[New way in dietotherapy of infants with food allergy].}, journal = {Voprosy pitaniia}, volume = {73}, number = {6}, pages = {32-35}, pmid = {15685857}, issn = {0042-8833}, mesh = {Animals ; Dermatitis, Atopic/*diet therapy/immunology ; Female ; Goats ; Humans ; Immunoglobulin E/blood/immunology ; Infant ; *Infant Food ; Male ; Milk/immunology ; Milk Hypersensitivity/*immunology ; Milk Proteins/*adverse effects ; }, abstract = {The authors followed up (in outpatient conditions) a total of fifty 1-to-9-mounth-old infants with the diagnosis of atopic dermatitis, disseminated form, of subacute course. The infants were followed up for 3-12 months, with 83% of the 113 examined patients 1-3 weeks after the beginning of treatment having shown clinical improvement of cutaneous inflammatory processes. Of the 172 infants subjected to immunological examination, in 100--the level of total IgE in blood serum was significantly elevated. These children also had elevated level of the specific IgE antibodies to cow's milk proteins. The outcomes of the carried out dietotherapy using mixture "Nanny" showed that this therapeutic product resulted in remission in the majority of the followed up infants suffering from allergy to cow's milk proteins.}, }
@article {pmid15665958, year = {2004}, author = {Denisova, NA and Pletneva, TV and Baikova, VN and Berezov, TT}, title = {Kinetic characteristics of biochemical parameters during consupren therapy after allogenic transplantation of the kidney.}, journal = {Bulletin of experimental biology and medicine}, volume = {138}, number = {4}, pages = {407-411}, pmid = {15665958}, issn = {0007-4888}, mesh = {Adolescent ; Adult ; Creatinine/blood ; Cyclosporine/administration & dosage/blood/*therapeutic use ; Female ; Humans ; Immunosuppressive Agents/administration & dosage/blood/*therapeutic use ; Kidney Transplantation/*physiology ; Kinetics ; Male ; Middle Aged ; Transplantation, Homologous ; Urea/blood ; }, abstract = {Changes in biochemical and common clinical parameters of the blood were detected in patients treated with consupren (cyclosporin) as the main immunosuppressant after allogenic transplantation of the kidney. Kinetic model for evaluation of treatment adequacy was based on therapeutic drug monitoring and monitoring of blood biochemistry in recipients of the primary kidney transplant. The k1, t1/2, C0, clearance (for hemoglobin), conditioned volume of distribution (for cyclosporin) of processes of biochemical parameters (toxicity markers) stabilization within the framework of a single-part kinetic model were determined.}, }
@article {pmid15651660, year = {2004}, author = {Smetannikova, MA and Beliavskaia, VA and Smetannikova, NA and Savkin, IV and Denisova, DV and Ustinov, SN and Maksimov, VN and Shabalin, AV and Bolotnova, TV and Voevoda, MI}, title = {[Functional polymorphism of p53 and CCR5 genes in the long-lived of the Siberian region].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {11}, pages = {25-28}, pmid = {15651660}, issn = {0869-6047}, mesh = {Aged ; Aged, 80 and over ; Alleles ; *Genes, p53 ; Humans ; Longevity/*genetics ; Polymorphism, Genetic ; Receptors, CCR5/*genetics ; Siberia ; }, abstract = {The P53 protein is a key regulator of modified-cell apoptosis. The functional oligonucleotide polymorphism of the p53 gene causes the substitution of arginine (Arg) for praline (Pro) in the codon 72. A reduced apoptotic activity of p53 and, as a consequence, development of oncology pathology is associated with the above polymorphism. CCR5 is a compound transmembrane receptor-protein, which apart from chemokines, binds with some molecules and is a coreceptor for HIV-1. 32 bp deletion within the CCR5 encoding region results in the loss of the protein's receptor function. It has been demonstrated that the transmission of the "external" (in respect to cell) stimulus, via the CCR5 system, induces expression of the p53 gene and initiates apoptosis. Allele variants and p53 and CCR5 genotypes (separately and in combinations) were investigated, within the present case study, for 131 long-livers from Novosibirsk and Tyumen Regions. A trend was detected towards accumulation of the p53 Pro alleles in association with the CCR5del32 allele in the study group, which, as the authors believe, can enhance the genome resistance to variable factors that cut the life span.}, }
@article {pmid15648924, year = {2004}, author = {Denisova, VV}, title = {[Detection of group-specific antigens of the ABO system in fish blood].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {47}, number = {6}, pages = {36}, pmid = {15648924}, issn = {0039-4521}, mesh = {*ABO Blood-Group System ; Animals ; *Blood Grouping and Crossmatching ; *Blood Stains ; Fishes/*blood ; Humans ; }, abstract = {The subject of the case study was blood of 8 fish species. It was examined within the ABO system. 68 tests of stains of fish blood mixed with human blood were made. It was shown as possible to differentiate between human blood and fish blood in mixed stains.}, }
@article {pmid15636146, year = {2004}, author = {Kozhagel'dieva, AA and Karal'nik, BV and Denisova, TG and Tugambaev, TI}, title = {[Development of immunoreagents for the diagnostics of intestinal yersiniosis by antigen-binding lymphocytes].}, journal = {Zhurnal mikrobiologii, epidemiologii, i immunobiologii}, volume = {}, number = {6}, pages = {73-76}, pmid = {15636146}, issn = {0372-9311}, mesh = {Animals ; Antigens, Bacterial/analysis ; Cross Reactions ; Diagnosis, Differential ; Gastroenteritis/blood/*diagnosis ; Lipopolysaccharides/administration & dosage/immunology ; Lymphocytes/*immunology ; Rabbits ; Rosette Formation/*methods ; Time Factors ; Yersinia Infections/blood/*diagnosis ; Yersinia enterocolitica/*immunology/isolation & purification ; }, abstract = {To diagnose intestinal yersiniosis, the detection of antigen-binding lymphocytes (ABL) with respect to Y. enterocolitica O3, O5 and O9 is proposed. Experiments on the immunization of rabbits with Y. enterocolitica LPS of these serovars revealed that immunoreagents, according to the data of cross antigen-dependent rosette formation and its inhibition, had species specificity (ABL of rabbits immunized with Y. enterocolitica did not interact with Salmonella, Shigella and Y. pseudotuberculosis antigens) and serovar specificity. Cross reactions in the detection of ABL by means of specific Y. enterocolitica O9 and Brucella melitensis immunoreagents in rabbits immunized with Y. enterocolitica were absent during the first days and could be detected only of day 25 after the injection of the immunogen. The method for the detection of ABL with the use of newly developed reagents could be used in clinics for the diagnostics of intestinal yersiniosis.}, }
@article {pmid15602436, year = {2004}, author = {Malinova, LI and Dovgalevskiĭ, PIa and Simonenko, GV and Denisova, TP and Tuchin, VV}, title = {[Effect of high concentrations of glucose on physiological parameters of platelets in patients with ischemic heart disease.].}, journal = {Kardiologiia}, volume = {44}, number = {11}, pages = {24-27}, pmid = {15602436}, issn = {0022-9040}, mesh = {*Blood Platelets ; Coronary Artery Disease ; Diabetes Mellitus, Type 2/blood ; Erythrocytes ; *Glucose ; Humans ; Insulin/blood ; Myocardial Ischemia ; }, abstract = {Analysis of functional state of the erythrocyte system was carried out in 45 patients with stable class II and III angina including those with concomitant non insulin dependent diabetes and in 15 practically healthy subjects. The analysis was made in the process of upsetting the balance of the erythrocyte system by incubation with high concentrations of glucose in vitro. Functional state of erythrocytes was assessed by construction of fragments of a phase portrait on a plane representing relationship between dimensions of erythrocytes, glucose concentration and rate of the above mentioned process.}, }
@article {pmid15496847, year = {2004}, author = {Ashurov, ZM and Synebogov, SV and Denisova, LB and Varfolomeeva, SR and Iniushkina, IV}, title = {[Non-Hodgkin's lymphoma of the Pirogov-Waldeyer pharyngeal ring].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {4}, pages = {54-55}, pmid = {15496847}, issn = {0042-4668}, mesh = {Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Head and Neck Neoplasms/diagnosis/drug therapy/pathology ; Humans ; *Lymphoma, B-Cell/diagnosis/drug therapy/pathology ; Male ; *Nasopharyngeal Neoplasms/diagnosis/drug therapy/pathology ; *Tonsillar Neoplasms/diagnosis/drug therapy/pathology ; Treatment Outcome ; }, }
@article {pmid15458209, year = {2004}, author = {Lunkina, AV and Denisova, GA and Derenko, MV and Malarchuk, BA}, title = {[Mitochondrial DNA variation in two Russian populations from Novgorod oblast].}, journal = {Genetika}, volume = {40}, number = {7}, pages = {975-980}, pmid = {15458209}, issn = {0016-6758}, mesh = {DNA, Mitochondrial/*genetics ; *Genetics, Population ; Haplotypes ; Humans ; Russia ; }, abstract = {Mitochondrial DNA (mtDNA) polymorphism was examined in two Russian populations of Novgorod oblast, from the city of Velikii Novgorod (n = 81), and the settlement of Volot (n = 79). This analysis showed that the mitochondrial gene pool of Russians examined was represented by the mtDNA types belonging to 20 haplogroups and subhaplogroups distributed predominantly among the European populations. Haplogroups typical of the indigenous populations of Asia were found in the population sample from Velikii Novgorod with the average frequency of 3.7% (haplogroups A, Z, and D5), and with the frequency of 6.3% (haplogroups Z, D, and M*) in the Volot population. It was demonstrated that the frequency of the mitochondrial lineages combination, D5, Z, U5b-16144, and U8, typical of the Finnish-speaking populations of Northeastern Europe, was somewhat higher in the urban population (7.4%) compared to rural one (3.8%). The problem of genetic differentiation of Russians from Eastern Europe inferred from mtDNA data, is discussed.}, }
@article {pmid15380649, year = {2004}, author = {Shamtsyan, M and Konusova, V and Maksimova, Y and Goloshchev, A and Panchenko, A and Simbirtsev, A and Petrishchev, N and Denisova, N}, title = {Immunomodulating and anti-tumor action of extracts of several mushrooms.}, journal = {Journal of biotechnology}, volume = {113}, number = {1-3}, pages = {77-83}, doi = {10.1016/j.jbiotec.2004.04.034}, pmid = {15380649}, issn = {0168-1656}, mesh = {Adjuvants, Immunologic/isolation & purification/*pharmacology ; Agaricales/*chemistry ; Animals ; Antineoplastic Agents/isolation & purification/*pharmacology ; Humans ; Melanoma/*drug therapy ; Mice ; Mice, Inbred CBA ; Neoplasm Transplantation ; Neutrophils/drug effects/metabolism ; Reactive Oxygen Species/metabolism ; Skin Neoplasms/*drug therapy ; }, abstract = {Aqueous extracts from fruit bodies and mycelia of various higher Basidiomycetes were studied in search for reliable biological effects. In vitro and in vivo experiments were conducted. The results showed that the aqueous extracts demonstrated various types of marked biological actions: an increased production of reactive oxygen forms by neutrophil cells of human peripheral blood; a significant mitogenic activity in a wide range of concentrations; stimulation on production of inflammatory cytokines interleukine 1-beta and interleukine-8 by peripheral blood cells; a decrease in both average tumor size in mice with transplanted melanoma B16 and a manifestation of tumorous intoxication; and a prolongation in the survival rate of such mice.}, }
@article {pmid15340341, year = {2004}, author = {Novikova, DS and Bekbosynova, MS and Antidze, TIa and Loladze, NV and Domogatskiĭ, SP and Golitsyn, SP and Nasonov, EL and Denisova, IA and Tonevitskiĭ, SP}, title = {[Autoantibodies Against beta(1)-Adrenoreceptors in Patients With Cardiac Rhythm Disorders. Prevalence and Possible Role in Development of Arrhythmia].}, journal = {Kardiologiia}, volume = {44}, number = {7}, pages = {17-22}, pmid = {15340341}, issn = {0022-9040}, mesh = {*Autoantibodies/blood ; Cardiomyopathy, Dilated ; Humans ; Myocarditis/immunology ; Prevalence ; *Receptors, Adrenergic, beta-1 ; }, abstract = {AIM: To assess prevalence of autoantibodies against beta(1)-adrenoreceptors (beta(1)-AR) in patients with arrhythmias of various etiology.

METHODS: Glass-ionomer dental cement samples, prepared with a standard amount of cement powder and different amounts of water have been examined after being hardened. Surface microstructure and ultrasound, longitudinal and shear velocities were obtained with a scanning acoustic microscope. Conditional effective elastic modulus and Poisson's ratio have been calculated using longitudinal and shear sound velocity values. Then on the same samples elastic modulus and microhardness have been determined by standard tests. Additional samples have been used to determine compressive strength.

RESULTS: Density; conditionally instantaneous elastic modulus; high-elasticity modulus and compression strength of the samples decrease when large amounts of water were used for their preparation. At the same time porosity and microhardness of the cement matrix increase. Acoustic parameters and parameters of elasticity, calculated on the basis of sound velocity, demonstrated changes, similar to those obtained in standard mechanical tests.

SIGNIFICANCE: The established relation between microstructure, acoustic and mechanical parameters demonstrated a high capacity of acoustic microscopy application for non-destructive characterization of dental materials. A particular advantage of the acoustic microscopy is the opportunity to evaluate microstructure and mechanical properties on the same sample.}, }
@article {pmid14870584, year = {2003}, author = {Zav'ialova, LG and Denisova, DV}, title = {[Nutrition and blood lipid profile in adolescents during socioeconomic reforms in Russia: epidemiological study].}, journal = {Voprosy pitaniia}, volume = {72}, number = {6}, pages = {18-24}, pmid = {14870584}, issn = {0042-8833}, mesh = {Adolescent ; Adolescent Nutritional Physiological Phenomena/*physiology ; Cross-Sectional Studies ; Dietary Carbohydrates/administration & dosage ; Dietary Fats/administration & dosage ; Dietary Proteins/administration & dosage ; Female ; Humans ; Hyperlipidemias/blood/*epidemiology/etiology ; Lipids/*blood ; Male ; Risk Factors ; Sex Factors ; Siberia/epidemiology ; Socioeconomic Factors ; Surveys and Questionnaires ; }, abstract = {Aim of study was to assess trends in lipid profile and nutrition of adolescent population in Novosibirsk during the social and economic reforms in Russia (1989-1999). Three cross-sectional studies of school aged 14-17 in 1989 (657), in 1994 (620) and in 1999 (626) were carried out. Total sample was 1903 (914 males and 989 females). Blood lipids, such as total cholesterol (TC0, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were measured. Diet was estimated with the method of 24-hour dietary recall. During 10-year period mean serum TC decreased from 175 to 158 mg/dl in males and from 191 to 175 mg/dl in females (p < 0.001 for both genders). Females had significantly higher mean NC than did males at all surveys (p < 0.001)/Between 1989 and 1994 mean HDL-C levels decreased in boys both (p < 0.001), but in 1999 these levels were similar to 1989. During 1989-1994, TG levels significantly decreased, but between 1994 and 1999 mean TG levels increased in 1.5 times in both gender groups. Prevalence of high TC (> = 2000 mg/dl) significantly decreased from 17% to 6% in males and from 28% to 14% in females. Frequencies of low HDL-C (> = 40 mg/dl) also decreased in boys (from 28 to 8%) and girls (from 13 to 3%). Trends in diet showed similar changes and characterized by significant decreasing of total energy intakes (from 3021 to 2342 kcal in boys and from 2300 to 1644 kcal in girls) and of basic nutrient intakes (proteins? Fats? Carbohydrates). Negative trends in blood lipid profile and diet in adolescents during the unstable period of socioeconomic reforms in Russia indicate on serious changes in metabolic processes and need in large state economic programs to improve the situation.}, }
@article {pmid14724672, year = {2004}, author = {Wang, Z and Troilo, PJ and Wang, X and Griffiths, TG and Pacchione, SJ and Barnum, AB and Harper, LB and Pauley, CJ and Niu, Z and Denisova, L and Follmer, TT and Rizzuto, G and Ciliberto, G and Fattori, E and Monica, NL and Manam, S and Ledwith, BJ}, title = {Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation.}, journal = {Gene therapy}, volume = {11}, number = {8}, pages = {711-721}, doi = {10.1038/sj.gt.3302213}, pmid = {14724672}, issn = {0969-7128}, mesh = {Animals ; DNA/administration & dosage/*metabolism ; Electroporation ; Erythropoietin/*genetics ; Genetic Therapy/*methods ; *Genome ; Injections, Intramuscular ; Mice ; Mice, Inbred BALB C ; Polymerase Chain Reaction/methods ; Transfection/methods ; }, abstract = {Plasmid vectors have been widely used for DNA vaccines and gene therapy. Following intramuscular injection, the plasmid that persists is extrachromosomal and integration into host DNA, if it occurs at all, is negligible. However, new technologies for improving DNA delivery could increase the frequency of integration. In the present study, we tested the effect of electroporation on plasmid uptake and potential integration following intramuscular injection in mice, using a plasmid containing the mouse erythropoietin gene. Electroporation increased plasmid tissue levels by approximately six- to 34-fold. Using a quantitative gel-purification assay for integration, electroporation was found to markedly increase the level of plasmid associated with high-molecular-weight genomic DNA. To confirm integration and identify the insertion sites, we developed a new assay - referred to as repeat-anchored integration capture (RAIC) PCR - that is capable of detecting rare integration events in a complex mixture in vivo. Using this assay, we identified four independent integration events. Sequencing of the insertion sites suggested a random integration process, but with short segments of homology between the vector breakpoint and the insertion site in three of the four cases. This is the first definitive demonstration of integration of plasmid DNA into genomic DNA following injection in vivo.}, }
@article {pmid14597392, year = {2003}, author = {Denisov, DA and Denisova, GF}, title = {Hierarchical structure of donor splice site sequence multitude.}, journal = {Gene}, volume = {320}, number = {}, pages = {89-96}, pmid = {14597392}, issn = {0378-1119}, mesh = {Alternative Splicing/*genetics ; Base Sequence ; Binding Sites/genetics ; Evolution, Molecular ; Exons/genetics ; Introns/genetics ; Models, Genetic ; *Phylogeny ; Point Mutation ; }, abstract = {An analysis of donor splice site sequence (dsss) multitude was carried out. A special method was developed to study the multitude properties. The multitude of dsss was arranged as a hierarchical tree where the "root" consists of a small group of "ancestors", VAGgtVAG (gt stands in the beginning of intron, V=C,A,G). Every ancestor has its own clan of "descendants" which represent point mutants of it. The latter are split into "progenies". The first progeny looks like point mutants of the ancestors, the second as one-point mutants of sequences of the first progeny, and so forth. This picture looks like a hierarchical phylogenetic tree. The most striking property of the multitude is the successive monotonic decrease in occurrences of the sequences from one progeny to another. It is shown that such results may be modeled by a virtual mutational process.}, }
@article {pmid14596802, year = {2003}, author = {Enshell-Seijffers, D and Denisov, D and Groisman, B and Smelyanski, L and Meyuhas, R and Gross, G and Denisova, G and Gershoni, JM}, title = {The mapping and reconstitution of a conformational discontinuous B-cell epitope of HIV-1.}, journal = {Journal of molecular biology}, volume = {334}, number = {1}, pages = {87-101}, pmid = {14596802}, issn = {0022-2836}, mesh = {Algorithms ; Amino Acid Sequence ; Amino Acids/chemistry ; Antibodies, Monoclonal/immunology/metabolism ; B-Lymphocytes/*immunology ; *Epitopes ; HIV-1/*chemistry/*immunology ; Humans ; Models, Molecular ; Peptide Library ; *Protein Conformation ; }, abstract = {A method for the discovery of the structure of conformational discontinuous epitopes of monoclonal antibodies (mAbs) is described. The mAb is used to select specific phages from combinatorial phage-display peptide libraries that in turn are used as an epitope-defining database that is applied via a novel computer algorithm to analyze the crystalline structure of the original antigen. The algorithm is based on the following: (1) Most contacts between a mAb and an antigen are through side-chain atoms of the residues. (2) In the three-dimensional structure of a protein, amino acid residues remote in linear sequence can juxtapose to one another through folding. (3) Tandem amino acid residues of the selected phage-displayed peptides can represent pairs of juxtaposed amino acid residues of the antigen. (4) Contact residues of the epitope are accessible to the antigen surface. (5) The most frequent tandem pairs of amino acid residues in the selected phage-displayed peptides can reflect pairs of juxtaposed amino acid residues of the epitope. Application of the algorithm enabled prediction of epitopes. On the basis of these predictions, segments of an antigen were used to reconstitute an antigenic epitope mimetic that was recognized by its original mAb.}, }
@article {pmid14515635, year = {2003}, author = {Panov, VO and Nadtochiĭ, AG and Ivanov, AV and Inaneishvili, MG and Denisova, LB and Safiullina, IM}, title = {[Magnetic resonance imaging and ultrasound study in the diagnosis og facial angiodysplasias in children: competition or collaboration?].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {3}, pages = {13-19}, pmid = {14515635}, issn = {0042-4676}, mesh = {Adolescent ; Adult ; Angiodysplasia/*diagnosis/diagnostic imaging ; Child ; Child, Preschool ; Face ; Female ; Humans ; Infant ; *Magnetic Resonance Angiography ; Male ; Sensitivity and Specificity ; Ultrasonography, Doppler, Color ; }, abstract = {This study deals with the capacities of noninvasive magnetic resonance imaging (MRI) with magnetic resonance angiography (MRA) without administration of magnetic resonance contrast substances in the diagnosis of facial soft tissue angiodysplasias in children. Indications for their use are defined. The methodology of the studies is proposed. Their diagnostic role and relationship with the other noninvasive technique of medical visualization--ultrasound study (USS) with Doppler color mapping (DCM) are assessed. As compared with USS, MRI may more accurately and objectively establish the organotopic characteristics of facial soft tissue angiodysplasias and detect lesions of the deep facial parts, maxillary bones, and paranasal sinuses in the diagnosis of these abnormalities. The use of MRI may define the belonging of angiodysplasias to the arterial or venous bed, reveal afferent and efferent vessels, including intracranial ones, and to detect intracranial angiodysplastic changes. USS with DSM was superior to MRI with MRA in defining functional (hemodynamic) parameters of angiodysplasias, which makes this method indispendable in planning treatment and in evaluating its efficiency. Comprehensive examination of patients with large and extensive angiodysplasias of facial soft tissues has indicated that facial angiodysplasias are external manifestations of a more generalized angiodysplastic process in most cases, which, in large and extensive facial angiodysplasias, makes it expedient to perform MRI with MRA of the brain and, if possible, the whole body. The high informative value of MRI with MRA in studying angiodysplasias makes them the method of choice in the diagnosis of this group of diseases.}, }
@article {pmid12943795, year = {2003}, author = {Denisova, G and Lideman, L and Spectorman, E and Abulafia-Lapid, R and Burke, M and Yust, I and Gershoni, JM}, title = {Characterization of new monoclonal antibodies that discriminate between soluble and membrane CD4 and compete with human anti-CD4 autoimmune sera.}, journal = {Molecular immunology}, volume = {40}, number = {5}, pages = {231-239}, pmid = {12943795}, issn = {0161-5890}, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; Autoantibodies/*immunology ; CD4 Antigens/classification/genetics/*immunology ; HIV Envelope Protein gp120/immunology ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; }, abstract = {In this report we present results on immunization of hu-CD4 C57Black/6J transgenic mice with HIV-1 gp120(451) complexed with its receptor protein, CD4. In addition to development of anti-gp120 antibodies, these mice also produced two anti-CD4 monoclonal antibodies, designated T6 and T9. Both these antibodies recognize soluble CD4 but not membrane associated CD4. Their corresponding epitopes map to the D3-D4 domains of CD4. These characteristics are very similar to the HIV related anti-CD4 autoimmunity found in 10-15% of HIV-1 infected people. Therefore, 208 HIV-1 positive patients were screened for anti-CD4 humoral response of which 27 were found positive (13%). Sixteen of these patients were then tested for their ability to compete with the T6 and T9 anti-CD4 monoclonal antibodies. In such experiments saturating amounts of either T6 or T9 antibodies were able to prevent 20-80% of the human serum binding to immobilized soluble CD4 in competitive ELISA tests. The T6 and T9 antibodies therefore help to define distinct CD4 epitopes associated with clinical anti-CD4 autoimmunity.}, }
@article {pmid12940914, year = {2003}, author = {Derenko, MV and Grzybowski, T and Malyarchuk, BA and Dambueva, IK and Denisova, GA and Czarny, J and Dorzhu, CM and Kakpakov, VT and Miścicka-Sliwka, D and Woźniak, M and Zakharov, IA}, title = {Diversity of mitochondrial DNA lineages in South Siberia.}, journal = {Annals of human genetics}, volume = {67}, number = {Pt 5}, pages = {391-411}, pmid = {12940914}, issn = {0003-4800}, mesh = {*DNA, Mitochondrial ; *Genetic Variation ; Humans ; Phylogeny ; Polymorphism, Restriction Fragment Length ; Siberia/epidemiology ; }, abstract = {To investigate the origin and evolution of aboriginal populations of South Siberia, a comprehensive mitochondrial DNA (mtDNA) analysis (HVR1 sequencing combined with RFLP typing) of 480 individuals, representing seven Altaic-speaking populations (Altaians, Khakassians, Buryats, Sojots, Tuvinians, Todjins and Tofalars), was performed. Additionally, HVR2 sequence information was obtained for 110 Altaians, providing, in particular, some novel details of the East Asian mtDNA phylogeny. The total sample revealed 81% East Asian (M*, M7, M8, M9, M10, C, D, G, Z, A, B, F, N9a, Y) and 17% West Eurasian (H, U, J, T, I, N1a, X) matrilineal genetic contribution, but with regional differences within South Siberia. The highest influx of West Eurasian mtDNAs was observed in populations from the East Sayan and Altai regions (from 12.5% to 34.5%), whereas in populations from the Baikal region this contribution was markedly lower (less than 10%). The considerable substructure within South Siberian haplogroups B, F, and G, together with the high degree of haplogroup C and D diversity revealed there, allows us to conclude that South Siberians carry the genetic imprint of early-colonization phase of Eurasia. Statistical analyses revealed that South Siberian populations contain high levels of mtDNA diversity and high heterogeneity of mtDNA sequences among populations (Fst = 5.05%) that might be due to geography but not due to language and anthropological features.}, }
@article {pmid12939834, year = {2003}, author = {Denisova, OP and Pigolkin, IuI and Bogomolov, DV and Dolzhanskiĭ, OV and Bogomolova, IN and Gornostaev, DV}, title = {[Forensic and medical evaluation of vascular malformations of the brain in cranio-cerebral trauma].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {46}, number = {4}, pages = {6-10}, pmid = {12939834}, issn = {0039-4521}, mesh = {Adult ; Algorithms ; Brain/*blood supply/physiopathology ; Cerebral Hemorrhage/etiology ; Cerebrovascular Disorders/*etiology ; Craniocerebral Trauma/*complications/physiopathology ; Fatal Outcome ; *Forensic Medicine ; Humans ; Male ; }, abstract = {A classification of vascular malformations (VM) is defined in the article including a differentiation between their macroscopic and histological variations; an independently-authors-observed case of arterial-and-venous malformation (AVM) in a minor cranial-cerebral trauma (CCT) is described. Published data reflecting the forensic-and-medical value of AVM and cavernous malformations as well as of telangectasias and of arterial-and-venous fistulas in minor head traumas are analyzed. Issues of the forensic-and-medical expertise of VM and remote consequences of CCT are under consideration. VM are assessed in CCT patients with epilepsy and other pathologies. An algorithm of the forensic medical expertise of VM is suggested.}, }
@article {pmid12926342, year = {2003}, author = {Portnoĭ, LM and Denisova, LB and Utkina, EV and Safiullina, IM and Denisov, VA and Sachechelashvili, GL}, title = {[Magnetic-resonance tomography in diagnosis of hepatopancreatoduodenal tumors].}, journal = {Khirurgiia}, volume = {}, number = {7}, pages = {59-65}, pmid = {12926342}, issn = {0023-1207}, mesh = {Adult ; Aged ; Cholangiopancreatography, Endoscopic Retrograde ; Female ; Gastrointestinal Neoplasms/complications/*diagnosis ; Humans ; Jaundice, Obstructive/diagnosis/etiology ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Pancreatic Neoplasms/complications/*diagnosis ; Tomography/*methods ; }, abstract = {Results of magnetic-resonance tomography (MRT) in 112 patients with diseases of hepatopancreatoduodenal zone were analyzed, 24 of them had tumors of bile ducts and pancreas. New noninvasive diagnostic method--magnetic-resonance cholangiopancreatography (MRCPG)--performed in addition to routine MRT was evaluated. The technique of MRCPG, analysis of results, manetic-resonance semiotics are presented. This method is compared with endoscopic retrograde cholangiopancreatography. It is concluded that combination of consentional MRT with MRCPG increases possibilities in diagnosis of hepatopancreatoduodenal cancers, complicated by obstructive jaundice, as a rule.}, }
@article {pmid12886639, year = {2003}, author = {Denisova, TG and Karal'nik, BV and Urazov, VX and Kenzhebaeva, AT and Amireev, SA and Kuznetsova, EL and Vaneeva, NP}, title = {[Detection of lymphocytes binding erythrocytes conjugated with Salmonella antigens].}, journal = {Zhurnal mikrobiologii, epidemiologii, i immunobiologii}, volume = {}, number = {3}, pages = {79-80}, pmid = {12886639}, issn = {0372-9311}, mesh = {Animals ; *Antigen Presentation ; Antigens, Bacterial/*immunology/metabolism ; Erythrocytes/*immunology/metabolism ; Immunization ; Immunoassay ; Lymphocytes/*immunology ; Rabbits ; Salmonella typhi/*immunology ; }, abstract = {Immune reagents for the detection of specific antigen-binding lymphocytes (ABL) with respect to different Salmonells antigens were developed. Rabbits were immunized with killed S. typhi and other salmonellae containing cross-reacting antigens, and the dynamics of the formation of ASL of each specificity was studied. Differences in the time of the appearance of ASL with receptors to thymus-independent (09, 12 or Vi) and thymus-dependent (Hd) antigens were studied. The relative content of ASL, determined with the use of immune reagents prepared from S. typhi antigens, was higher, on the whole, in rabbits immunized with S. typhi than in rabbits immunized with salmonellae containing one of cross-reacting antigens (S. enteritidis--09, 12; S. paratyphi C--Vi; S. virginia--Hd).}, }
@article {pmid12819786, year = {2003}, author = {Carrasco, M and McElree, B and Denisova, K and Giordano, AM}, title = {Speed of visual processing increases with eccentricity.}, journal = {Nature neuroscience}, volume = {6}, number = {7}, pages = {699-700}, doi = {10.1038/nn1079}, pmid = {12819786}, issn = {1097-6256}, support = {R01 MH057458/MH/NIMH NIH HHS/United States ; R01 MH057458-03/MH/NIMH NIH HHS/United States ; MH57458/MH/NIMH NIH HHS/United States ; }, mesh = {Differential Threshold ; Discrimination Learning ; Fovea Centralis/physiology ; Humans ; Motion Perception/*physiology ; Orientation ; Photic Stimulation ; *Psychophysics ; Random Allocation ; Reaction Time ; Sensory Thresholds ; Visual Fields/*physiology ; Visual Perception/*physiology ; }, abstract = {The visual system has a duplex design to meet conflicting environmental demands: the fovea has the resolution required to process fine spatial information, but the periphery is more sensitive to temporal properties. To investigate whether the periphery's sensitivity is partly due to the speed with which information is processed, we measured the full timecourse of visual information processing by deriving joint measures of discriminability and speed, and found that speed of information processing varies with eccentricity: processing was faster when same-size stimuli appeared at 9 degrees than 4 degrees eccentricity, and this difference was attenuated when the 9 degrees stimuli were magnified to equate cortical representation size. At the same eccentricity, larger stimuli are processed more slowly. These temporal differences are greater than expected from neurophysiological constraints.}, }
@article {pmid12793519, year = {2003}, author = {Joseph, JA and Denisova, NA and Arendash, G and Gordon, M and Diamond, D and Shukitt-Hale, B and Morgan, D}, title = {Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model.}, journal = {Nutritional neuroscience}, volume = {6}, number = {3}, pages = {153-162}, doi = {10.1080/1028415031000111282}, pmid = {12793519}, issn = {1028-415X}, mesh = {Alzheimer Disease/*drug therapy/genetics/physiopathology ; Amyloid beta-Peptides/analysis ; Amyloid beta-Protein Precursor/genetics ; Animals ; *Behavior, Animal ; *Blueberry Plants ; Brain/enzymology ; *Diet ; Disease Models, Animal ; *Fruit ; GTP Phosphohydrolases/metabolism ; Genetic Predisposition to Disease ; Membrane Proteins/genetics ; Memory ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Mitogen-Activated Protein Kinases/metabolism ; Neurons/physiology ; Phytotherapy ; Plant Extracts/therapeutic use ; Presenilin-1 ; Protein Kinase C/metabolism ; Protein Kinase C-alpha ; *Signal Transduction ; Sphingomyelins/metabolism ; Type C Phospholipases/metabolism ; }, abstract = {Previously, we showed that blueberry (BB) supplementation reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BB-fed (from 4 months of age) APP + PS1 transgenic mice showed no deficits in Y-maze performance (at 12 months of age) with no alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced enhancement of memory-associated neuronal signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.}, }
@article {pmid12751249, year = {2003}, author = {Bel'kova, NL and Parfenova, VV and Kostopnova, TIa and Denisova, LIa and Zaĭchikov, EF}, title = {[Microbial biodiversity in the Lake Baikal water].}, journal = {Mikrobiologiia}, volume = {72}, number = {2}, pages = {239-249}, pmid = {12751249}, issn = {0026-3656}, mesh = {Acetobacteraceae/genetics/isolation & purification ; Actinobacteria/genetics/isolation & purification ; Bacteria/cytology/genetics/*isolation & purification ; Cyanobacteria/genetics/isolation & purification ; Fresh Water/*microbiology ; Gene Silencing ; Gram-Negative Anaerobic Bacteria/genetics/isolation & purification ; Microscopy, Electron ; Phylogeny ; Proteobacteria/genetics/isolation & purification ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/genetics ; Russia ; }, abstract = {The investigation of the microbial community of Lake Baikal by the methods of general and molecular microbiology showed that culturable bacterial strains were represented by various known genera. The lake water contains a great number of bacterial morphotypes, as revealed by electron microscopy, and a great diversity of nonculturable microorganisms belonging to different phylogenetic groups, as revealed by 16S rRNA gene fragment sequencing. The inference is made that the microbial community of Lake Baikal contains not only the known species but also new, possibly endemic to the lake, bacterial species.}, }
@article {pmid12722358, year = {2003}, author = {Denisova, DA and Pureskin, NP}, title = {[Loss of visual function as the result of gunshot injuries of the eye].}, journal = {Voenno-meditsinskii zhurnal}, volume = {324}, number = {2}, pages = {20-2, 78}, pmid = {12722358}, issn = {0026-9050}, mesh = {Eye Injuries/complications/etiology/surgery ; Military Medicine ; Military Personnel ; Retrospective Studies ; USSR ; Vision Disorders/*etiology ; Warfare ; Wounds, Gunshot/*complications ; }, abstract = {The article presents the clinical-and-statistical analysis of causes of visual function loss occurred after the gunshot injuries of eyes. The main cause of sight loss is the eye destruction as the result of gunshot injury (61.1%). Because of the unsuccessful treatment of posttraumatic changes in eyeball the injured eyes were removed in 38.9% of the casualties. In most cases the fragmentation and mine-explosive trauma were the cause of eye destruction. In the cases of eyeball destruction enucleation and evisceration were the main surgical interventions. In the therapy of posttraumatic changes in the injured eye (flaccid inflammatory process without tendency towards its resolution, painful syndrome as well as eyeball atrophy and subatrophy) enucleation was performed. Improvement of conservative methods in therapy of posttraumatic complications could contribute to decrease in the number of casualties with sight loss after the eye gunshot injures.}, }
@article {pmid12717908, year = {2000}, author = {Portnoĭ, LM and Kazantseva, IA and Stashuk, GA and Gaganov, LE and Denisova, LB and Nefedova, VO and Legostaeva, TB and Iaurova, NV}, title = {[Current X-ray diagnosis of stomach cancer (comparison of radiologic and morphological methods of investigation)].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {6}, pages = {19-29}, pmid = {12717908}, issn = {0042-4676}, mesh = {Aged ; Female ; Gastroscopy ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Stomach/pathology ; Stomach Neoplasms/*diagnosis/diagnostic imaging/*pathology ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {By using the principles of wide comparisons of the data of radiation diagnosis (routine X-ray study, ultrasonography (USG), CT, MRI) with the morphological findings of resected gastric specimens from patients with endophytic gastric cancer (EGC) (n = 85), the authors propose some points in the problem associated with its diagnosis. They believe that by taking into account the fact that there is an obvious growth of endophytic parietally growing gastric cancer with the concurrent reduction in its intestinal forms, it is necessary to restore current radiation to its leading place, along with endoscopy, in detecting the cancer. The authors makes a highly positive assessment of USG, CT, MRI in addition to routine X-ray study and endoscopy particularly in those cases when difficulties emerge in histological verification of the existing signs of parietally growing cancer. The paper makes indications for USG, CT, MRI concrete. The authors also show how to stage gastric cancer.}, }
@article {pmid12717891, year = {1999}, author = {Denisova, LB and Vorontsova, SV and Shvedov, VA}, title = {[On the diagnosis of congenital toxoplasmosis].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {1}, pages = {45-47}, pmid = {12717891}, issn = {0042-4676}, mesh = {Female ; Humans ; Middle Aged ; Toxoplasmosis, Congenital/*diagnosis ; }, }
@article {pmid12622038, year = {2002}, author = {Chekunova, EV and Denisova, LB and Bazaev, VV}, title = {[Algorithms of diagnostic radiation methods in current urological pathology].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {46-49}, pmid = {12622038}, issn = {0042-4676}, mesh = {*Algorithms ; Angiography/methods ; Humans ; Radioisotope Renography/methods ; Ultrasonography ; Urography/methods ; Urologic Diseases/*diagnosis/diagnostic imaging ; }, abstract = {Based on the results of 3600 studies using all basic methods of modern radiation diagnosis, the authors show it necessary to develop diagnostic algorithms applicable to certain groups of urological diseases (urolithiasis, inflammatory processes and bulky masses in the kidney). This necessity has recently stemmed from the advent of new technologies of radiation diagnosis and from the expediency of using a certain method at the specific stage of examination. At the same time, the authors underline the importance of using standardized examination programmes (algorithms) in practice, which is also due to the fact that unreasonable use of the whole set of new radiation techniques that are of highly diagnostic value may bear great material costs.}, }
@article {pmid12596516, year = {2002}, author = {Bol'shakov, VV and Sapozhkov, AV and Denisova, SV}, title = {[Effect of droperidol and tramadol combination on the hemostasis in rabbits].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {65}, number = {5}, pages = {50-52}, pmid = {12596516}, issn = {0869-2092}, mesh = {Analgesics, Opioid/administration & dosage/*adverse effects ; Animals ; Antipsychotic Agents/administration & dosage/*adverse effects ; Dose-Response Relationship, Drug ; Droperidol/administration & dosage/*adverse effects ; Drug Combinations ; Female ; Hemostasis/*drug effects ; Male ; Rabbits ; Tramadol/administration & dosage/*adverse effects ; }, abstract = {The effect of a combined administration of analgesic droperidol and neuroleptic tramadol (tramal) on the plasma coagulation and platelet aggregation was studied on awake rabbits. Both tramadol and droperidol, as well as their combination, enhance the coagulation of plasma proteins and suppress the thrombocyte deaggregation process.}, }
@article {pmid12500679, year = {2002}, author = {Maliarchuk, BA and Derenko, MV and Grzybowski, T and Czarny, J and Miscicka-Slivka, D and Denisova, GA and Kostiunina, EA}, title = {[Mitochondrial DNA variation in Russian populations of Stavropol krai, Orel and Saratov oblasts].}, journal = {Genetika}, volume = {38}, number = {11}, pages = {1532-1538}, pmid = {12500679}, issn = {0016-6758}, mesh = {*DNA, Mitochondrial ; Dagestan/ethnology ; *Genetic Variation ; *Genetics, Population ; Haplotypes/genetics ; Humans ; Russia/ethnology ; }, abstract = {Mitochondrial DNA (mtDNA) polymorphism was examined in three Russian populations from the European part of Russia (Stavropol krai, Orel oblast, and Saratov oblast). This analysis showed that mitochondrial gene pool of Russians was represented by the mtDNA types belonging to haplogroups H, V, HV*, J, T, U, K, I, W, and X. A mongoloid admixture (1.5%) was revealed in the form of mtDNA types of macrohaplogroup M. Comparative analysis of the mtDNA haplogroup frequency distribution patterns in six Russian populations from the European part of Russia indicated the absence of substantial genetic differences between them. However, in Russian populations from the southern and central regions the frequency of haplogroup V (average frequency 8%) was higher than in the populations from more northern regions. Based on the data on mtDNA HVS1 sequence variation, it was shown that the diversity of haplogroup V in Russians (h = 0.72) corresponded to the highest h values observed in Europe. The reasons for genetic differentiation of the Russian population (historical, ecological, and adaptive) are discussed.}, }
@article {pmid12499999, year = {2003}, author = {Reshetnikov, OV and Denisova, DV and Zavyalova, LG and Häivä, VM and Granberg, C}, title = {Helicobacter pylori seropositivity among adolescents in Novosibirsk, Russia: prevalence and associated factors.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {36}, number = {1}, pages = {72-76}, pmid = {12499999}, issn = {0277-2116}, mesh = {Adolescent ; Age Distribution ; Enzyme-Linked Immunosorbent Assay ; Female ; Helicobacter Infections/*blood/*epidemiology/immunology ; Helicobacter pylori/*immunology ; Humans ; Life Style ; Male ; Odds Ratio ; Risk Factors ; Russia/epidemiology ; Seroepidemiologic Studies ; Sex Distribution ; Socioeconomic Factors ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: We have reported previously that infection is widespread among adults in Siberia, in whom prevalence rates range from 70% to 90%. The present study was undertaken to determine the seroprevalence of infection and its relation to social factors in a community-based population of adolescents in Novosibirsk, Western Siberia.

CONCLUSIONS: The prevalence of seropositivity among adolescents in Russia is higher than in developed countries. The infection is associated with lower socioeconomic status.}, }
@article {pmid12476838, year = {2002}, author = {Tsinberg, MB and Deriabin, DG and Denisova, IV}, title = {[Hygienic characterization of lactic acid bacteria products prepared by using hydrolysates of raw milk and soya bean materials].}, journal = {Gigiena i sanitariia}, volume = {}, number = {5}, pages = {54-56}, pmid = {12476838}, issn = {0016-9900}, mesh = {Animals ; Bacteria ; Cheese/*microbiology ; *Food Industry ; Humans ; Lactic Acid/*metabolism ; Milk/*metabolism/*microbiology ; Plant Lectins/*metabolism ; Protein Hydrolysates/*metabolism ; Soybean Proteins/*metabolism ; }, abstract = {The paper reflects the results of a comparative study of preparations of lactic acid bacteria (LAB), which are based on the hydrolysates of raw milk and soya bean materials, by using methods to determine the organoleptic and physicochemical properties, microbiological characteristics including the titer of microbial cells per ml of the preparation and the presence/absence of representatives of sanitary significant groups of microorganisms, the persistent properties of microorganisms. By summarizing the findings, it can be stated that it is possible to use a raw soya-bean hydrolysate-based nutrient medium to cultivate technical LAB strains with the compliance of the toxicological and microbiological parameters of the prepared preparations with the current sanitary standards. The LAB preparations grown on the hydrolysate-soya-bean medium have been protected with the patents of Russia. Their biological properties are highly competitive with those and, in some cases, superior to hydrolysate-milk medium-based preparations. This presents in their adhesive potential and in the formation of more pronounced antagonistic properties against opportunistic microorganisms.}, }
@article {pmid12452775, year = {2002}, author = {Denisova, NA and Shukitt-Hale, B and Rabin, BM and Joseph, JA}, title = {Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation.}, journal = {Radiation research}, volume = {158}, number = {6}, pages = {725-734}, pmid = {12452775}, issn = {0033-7587}, mesh = {Animals ; Behavior/*radiation effects ; Blotting, Western ; Body Weight/radiation effects ; Brain/*metabolism/pathology/*radiation effects ; Dopamine/metabolism ; Dose-Response Relationship, Radiation ; *Iron ; Male ; Maze Learning ; Memory/radiation effects ; Oxidative Stress ; Radiometry ; Rats ; Rats, Sprague-Dawley ; *Signal Transduction ; Synapses/metabolism ; Time Factors ; }, abstract = {Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.}, }
@article {pmid12449652, year = {2002}, author = {Derenko, MV and Maliarchuk, BA and Denisova, GA and Dambueva, IK and Kakpakov, VT and Dorzhu, ChM and Luzina, FA and Lotosh, EA and Ondar, UN and Kaplina, MI and Zakharov, IA}, title = {[Molecular genetic differentiation of ethnic populations in Southern and Eastern Siberia based on mitochondrial DNA polymorphism].}, journal = {Genetika}, volume = {38}, number = {10}, pages = {1409-1416}, pmid = {12449652}, issn = {0016-6758}, mesh = {Asian Continental Ancestry Group/genetics ; *DNA, Mitochondrial ; European Continental Ancestry Group/genetics ; Genetic Variation ; *Genetics, Population ; Humans ; Phylogeny ; *Polymorphism, Genetic ; Siberia/ethnology ; }, abstract = {Using the data on mitochondrial DNA (mtDNA) polymorphism, genetic structures of the ethnic groups inhabiting South and East Siberia, including Altaians, Buryats, Tuvinians, Todjins, Tofalars, Yakuts, and Evenks were described. Mitochondrial gene pools of the populations examined were characterized by different ratios between Mongoloid (M*, C, D, E/G, G, A, B, and F) and Caucasoid (H, HV, I, J, K, T, U, and X) mtDNA lineages. All the populations studied carried a marked Mongoloid component, maximum frequency of which was observed in Evenks (92.4%) and Buryats (90.1%). Maximum frequencies of Caucasoid mtDNA lineages were detected in Tofalars (20.7%) and Yakuts (14.5%). Statistically significant interpopulation differences regarding the frequencies of mtDNA haplogroups were observed between all populations examined, excluding the pairs of Evenks-Yakuts, Evenks-Tuvinians, and Tuvinians-Todjins. Differentiation of the ethnic groups inhabiting South and East Siberia, as well as Central and Middle Asia, is discussed based on genetic, linguistic, and anthropological data.}, }
@article {pmid12205156, year = {2002}, author = {Belousov, AB and Hunt, ND and Raju, RP and Denisova, JV}, title = {Calcium-dependent regulation of cholinergic cell phenotype in the hypothalamus in vitro.}, journal = {Journal of neurophysiology}, volume = {88}, number = {3}, pages = {1352-1362}, doi = {10.1152/jn.2002.88.3.1352}, pmid = {12205156}, issn = {0022-3077}, mesh = {Acetylcholine/*physiology ; Animals ; Bromodeoxyuridine ; Calcium/*physiology ; Cells, Cultured ; Hypothalamus/cytology/*physiology ; Neurons/*physiology ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission/physiology ; }, abstract = {Glutamate is a major fast excitatory neurotransmitter in the CNS including the hypothalamus. Our previous experiments in hypothalamic neuronal cultures showed that a long-term decrease in glutamate excitation upregulates ACh excitatory transmission. Data suggested that in the absence of glutamate activity in the hypothalamus in vitro, ACh becomes the major excitatory neurotransmitter and supports the excitation/inhibition balance. Here, using neuronal cultures, fura-2 Ca(2+) digital imaging, and immunocytochemistry, we studied the mechanisms of regulation of cholinergic properties in hypothalamic neurons. No ACh-dependent activity and a low number (0.5%) of cholinergic neurons were detected in control hypothalamic cultures. A chronic (2 wk) inactivation of N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors, L-type voltage-gated Ca(2+) channels, calmodulin, Ca(2+)/calmodulin-dependent protein kinases II/IV (CaMK II/IV), or protein kinase C (PKC) increased the number of cholinergic neurons (to 15-24%) and induced ACh activity (in 40-60% of cells). Additionally, ACh activity and an increased number of cholinergic neurons were detected in hypothalamic cultures 2 wk after a short-term (30 min) pretreatment with bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid tetrakis(acetoxy-methyl) ester (BAPTA AM; 2.5 microM), a membrane permeable Ca(2+)-chelating agent that blocks cytoplasmic Ca(2+) fluctuations. An increase in the number of cholinergic neurons following a chronic NMDA receptor blockade was likely due to the induction of cholinergic phenotypic properties in postmitotic noncholinergic neurons, as determined using 5-bromo-2'-deoxyuridine (BrdU) labeling. In contrast, a chronic inactivation of non-NMDA glutamate receptors or cGMP-dependent protein kinase had little effect on the expression of ACh properties. The data suggest that Ca(2+), at normal intracellular concentrations, tonically suppresses the development of cholinergic properties in hypothalamic neurons. However, a decrease in Ca(2+) influx into cells (through NMDA receptors or L-type Ca(2+) channels), inactivation of intracellular Ca(2+) fluctuations, or downregulation of Ca(2+)-dependent signal transduction pathways (CaMK II/IV and PKC) remove the tonic inhibition and trigger the development of cholinergic phenotype in some hypothalamic neurons. An increase in excitatory ACh transmission may represent a novel form of neuronal plasticity that regulates the activity and excitability of neurons during a decrease in glutamate excitation. This type of plasticity has apparent region-specific character and is not expressed in the cortex in vitro; neither increase in ACh activity nor change in the number of cholinergic neurons were detected in cortical cultures under all experimental conditions.}, }
@article {pmid12018172, year = {2002}, author = {Maliarchuk, BA and Derenko, MV and Denisova, GA and Nassiri, MR and Rogaev, EI}, title = {[Mitochondrial DNA polymorphism in populations of the Caspian region and southeastern Europe].}, journal = {Genetika}, volume = {38}, number = {4}, pages = {534-538}, pmid = {12018172}, issn = {0016-6758}, mesh = {Asian Continental Ancestry Group ; *DNA, Mitochondrial ; *Genetics, Population ; Humans ; Iran ; *Polymorphism, Genetic ; Russia/ethnology ; Turkmenistan ; Ukraine ; }, abstract = {Mitochondrial DNA (mtDNA) restriction polymorphism was examined in Turkmens, Eastern Iranians, and Ukrainians. The gene pools of all populations studied were characterized by the presence of European mtDNA lineages. Mongoloid component observed in Turkmen and Iranian populations with the frequencies of about 20% was represented by groups C, D, and E/G in Turkmens, and by M*, D, A, and B in Iranians. The relative positions of the populations studied, of populations from the Caucasus, Western Iran, and Russian populations from the Krasnodar krai and Belgorod oblast in the space of principal components revealed a geographically specific pattern of the population clustering. The data on mtDNA polymorphism indicated pronounced differentiation of Eastern and Western Iranians. The latter were characterized by a mtDNA group composition similar to that in Eastern Slavs. The historical role of the Caspian populations in the formation of the population of Southeastern Europe is discussed.}, }
@article {pmid11963568, year = {2002}, author = {Derenko, MV and Maliarchuk, BA and Denisova, GA and Dorzhu, ChM and Karamchakova, ON and Luzina, FA and Lotosh, EA and Dambueva, IK and Ondar, UN and Zakharov, IA}, title = {[Polymorphism of the Y-chromosome diallelic loci in the ethnic populations of the Altai-Sayan region].}, journal = {Genetika}, volume = {38}, number = {3}, pages = {393-399}, pmid = {11963568}, issn = {0016-6758}, mesh = {Alleles ; *Genetics, Population ; Haplotypes/genetics ; Humans ; Male ; *Polymorphism, Genetic ; Siberia/ethnology ; *Y Chromosome ; }, abstract = {Using the data on five biallellic Y-chromosome loci (DYS199, 92R7, SRY1532, RBF5 and DYS287) polymorphism, genetic structures of the five Turkic-speaking ethnic groups of the Altai-Sayan highland (Tuvinians, Sojots, Shorians, Khakassians, and Southern Altaians (Altai-Kizhi), were described. The gene pools of the populations examined were characterized by the presence of pronounced paleo-Caucasoid component (92R7-T-lineages). The frequency of this component increased westward, reaching more than 70% in Shorians and Southern Altaians. Haplotype TAT-C (RBF5 locus) was observed in all populations, except Shorians, with the frequencies varying from 5.4% in Altai-Kizhi to 18.8% in Khakassians. The Alu-insertion in the DYS287 locus was revealed only in the Altaian sample with the frequency of 3.3%. It was established that the Altai-Sayan populations studied split into two statistically significantly different groups. One of the groups was represented by Tuvinians, Sojots, and Khakassians, while another one was comprised of Shorians and Altaians.}, }
@article {pmid11958956, year = {2002}, author = {Hassan, WN and Cantuti-Castelevetri, I and Denisova, NA and Yee, AS and Joseph, JA and Paulson, KE}, title = {The nitrone spin trap PBN alters the cellular response to H(2)O(2): activation of the EGF receptor/ERK pathway.}, journal = {Free radical biology & medicine}, volume = {32}, number = {6}, pages = {551-561}, pmid = {11958956}, issn = {0891-5849}, support = {R01 DK 50442/DK/NIDDK NIH HHS/United States ; R01 GM 44634/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adaptor Proteins, Signal Transducing ; *Adaptor Proteins, Vesicular Transport ; Animals ; Calcium/metabolism ; Cyclic N-Oxides ; Drug Interactions ; Enzyme Activation ; Free Radical Scavengers/*pharmacology ; Hydrogen Peroxide/*pharmacology ; Mitogen-Activated Protein Kinases/*metabolism ; Nitrogen Oxides/*pharmacology ; PC12 Cells ; Phosphorylation/drug effects ; Proteins/metabolism ; Rats ; Receptor, Epidermal Growth Factor/*metabolism ; Shc Signaling Adaptor Proteins ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; }, abstract = {The nitrone spin trap PBN has been shown to protect neuronal cells from reactive oxygen species both in culture and in vivo. As an approach to understanding the molecular mechanisms by which PBN may function to protect cells, we examined whether PBN alters the cellular response to reactive oxygen species. H(2)O(2) stimulation of PC-12 cells results in weak activation of both the ERK and JNK signal transduction pathways. PBN pretreatment of PC-12 cells, followed by H(2)O(2) stimulation, results in strong and selective activation of the pro-survival ERK pathway. H(2)O(2) induction of ERK activity in PBN-pretreated cells was shown to be dependent on extracellular Ca(+2) influx. Further analysis of the ERK pathway showed that in PBN-pretreated cells, EGF receptor and the adapter protein SHC were phosphorylated in a Ca(+2)-dependent, ligand-independent manner following H(2)O(2) stimulation. Interestingly, H(2)O(2) stimulation of PBN-pretreated cells results in only 30% of the increase in intracellular Ca(+2) as compared to untreated cells following H(2)O(2) stimulation. These data suggest a model in which PBN attenuates H(2)O(2)-induced Ca(+2) entry, yet magnifies or alters Ca(+2) action, resulting in the activation of the EGF receptor/ERK pathway.}, }
@article {pmid11949255, year = {2002}, author = {Karal'nik, BV and Denisova, TG and Grushina, TA and Tugambaev, TI}, title = {[Analysis of immune response of guinea pigs infected with Brucella melitensis].}, journal = {Zhurnal mikrobiologii, epidemiologii, i immunobiologii}, volume = {}, number = {1}, pages = {52-56}, pmid = {11949255}, issn = {0372-9311}, mesh = {Animals ; Antigen Presentation ; *Brucella melitensis ; Brucellosis/*immunology ; Guinea Pigs ; *Immunity, Cellular ; T-Lymphocytes, Cytotoxic/*immunology ; }, abstract = {The dynamics of the first antigen specific stage of immune response to Brucella infection was experimentally studied with the method of binding adsorbed antigenic immunoreagents with lymphocytes. The study revealed that the content of antigen-binding lymphocytes (ABL) reached its maximum as early as on day 7 after infection, gradually decreasing afterwards (but even on day 90 ABL could be detected in the blood). The specificity of ABL was proved by the fact that they were absent in noninfected animals, while in the animals infected with Brucella their content was higher than that of ABL specific to Yersinia enterocolitica O9; Brucella-specific ABL bound Brucella lipopolysaccharide (LPS) more intensively than Yersinia LPS. The detection of Brucella-specific ABL was inhibited by Brucella LPS more actively than by Yersinia LPS. The evaluation of the affinity of ABL to homologous LPS, made by the ratio of binding immunoreagents of the same specificity, but with suboptimal and optimal specificity, proved that an increase in the avidity of ABL occurred in the dynamics of the infectious process, which corresponded to the increase of their specificity.}, }
@article {pmid11899837, year = {2002}, author = {Reshetnikov, OV and Kurilovich, SA and Tereshonok, IN and Denisova, DV and Zav'ialova, LG and Krivenchuk, NA and Zimina, IIu and Granberg, C and Häivä, VM}, title = {[Dyspepsia and gastroesophageal reflux in adolescents].}, journal = {Terapevticheskii arkhiv}, volume = {74}, number = {2}, pages = {9-13}, pmid = {11899837}, issn = {0040-3660}, mesh = {Adolescent ; Dyspepsia/complications/*epidemiology/microbiology ; Female ; Gastroesophageal Reflux/complications/*epidemiology ; Helicobacter pylori ; Humans ; Male ; }, abstract = {AIM: To study the prevalence and risk factors for dyspepsia and gastroesophageal reflux (GER) among adolescents.

MATERIAL AND METHODS: Senior schoolchildren (forms 9-11) of four randomly selected secondary schools of Novosibirsk participated in the study (189 boys and 260 girls aged 14-17 years). They filled in the Bowel Disease Questionnaire, and sera were tested for antibodies against Helicobacter pylori infection.

RESULTS: Dyspepsia was reported by 21% of the schoolchildren, being more frequent in girls (25%) than boys (14%, p = 0.004). GER occurred in 22% of adolescents with the same frequency in both genders. The combination of dyspepsia with GER was found in 8%. The prevalence of H. pylori infection was 56%. No association was found between the infection and abdominal symptoms, except heartburn. Among factors associated with dyspepsia were female gender, irregular meals, family history of dyspepsia. GER was related to H. pylori infection, obesity, smoking and irregular meals, 46% of adolescents with dyspepsia and 36% of those with GER have consulted a physician, and school absenteeism was reported by 55 and 40%, respectively.

CONCLUSION: Dyspepsia and gastroesophageal reflux are widespread among the adolescent population and result in frequent use of health care resources.}, }
@article {pmid11889863, year = {2002}, author = {Denisova, LA and Nasyrova, NV and Maev, RG and Grigor'ian, AS and Grigor'iants, LA and Denisov, AA and Grineva, TV and Maeva, EIu and Severin, FM}, title = {[Acoustic microscopy methods in studies of the filling materials microstructure].}, journal = {Stomatologiia}, volume = {81}, number = {1}, pages = {26-30}, pmid = {11889863}, issn = {0039-1735}, mesh = {Acoustics ; Dental Cements/*analysis ; Humans ; Microscopy, Electron, Scanning/instrumentation/*methods ; }, abstract = {The structure of filling materials (kemfil, polyacrylate cement, and Dentis, material produced by Stomadent Firm in Russia) at the interface with human dentin was studied in teeth subjected to retrograde filling with preliminary appendectomy. A prototype of table wide-field short pulse scanning acoustic microscope (50 mHz) (Acoustic Microscopy Center, Institute of Biochemical Physics of Russian Academy of Sciences) and Elsam acoustic microscope (200 mHz) (Leitz, Germany) were used. The results indicate that analysis of acoustic characteristics, including the data of acoustic microscopy, helps investigate the cement microstructure and evaluate the compactness and elasticity of samples; moreover, structural elements of the material, which are undetectable by other methods, are seen on acoustic images. These data can be used for evaluating the relationship between the microstructure and formation of mechanical properties, and, maybe, the patterns of cement interactions with dental tissues.}, }
@article {pmid11879960, year = {2002}, author = {Maev, RG and Denisova, LA and Maeva, EY and Denissov, AA}, title = {New data on histology and physico-mechanical properties of human tooth tissue obtained with acoustic microscopy.}, journal = {Ultrasound in medicine & biology}, volume = {28}, number = {1}, pages = {131-136}, pmid = {11879960}, issn = {0301-5629}, mesh = {*Acoustics ; Humans ; Tooth/*anatomy & histology/*diagnostic imaging ; *Ultrasonography ; }, abstract = {Quantitative evaluation of human tooth structural elements, revealed in acoustic images, has been carried out. It has been shown that tissue elements with different acoustic impedances differed in acoustic images by intensity of grey color, and also feature with different longitudinal sound velocities (C(L)). In the layer of mantle dentin, C(L) is 7% to 8% lower than in bulk dentin, and in the layer of dentin around the pulp chamber, C(L) is 15% lower. In carious enamel and dentin, C(L) decreases up to 7% to 17%. In pathologic teeth, dentin areas with higher density can be revealed; they feature higher C(L); in transparent dentin C(L) can be 15% to 20% higher than in bulk dentin. Results of the present study show that acoustic images reflect internal biomechanical properties of tooth tissue microstructure that can be evaluated quantitatively by means of longitudinal sound velocity determination.}, }
@article {pmid11767501, year = {2001}, author = {Denisova, L and Vorontsova, S and Safiullina, I and Emel'ianova, L}, title = {[X-ray diagnosis of the adrenal neoplasms].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {41-48}, pmid = {11767501}, issn = {0042-4676}, mesh = {Adrenal Gland Diseases/*diagnosis/surgery ; Adrenal Gland Neoplasms/*diagnosis/diagnostic imaging/surgery ; Adult ; Cysts/*diagnosis/surgery ; Female ; Ganglioneuroma/*diagnosis/diagnostic imaging/surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Myelolipoma/*diagnosis/diagnostic imaging/surgery ; Tomography, X-Ray Computed ; Ultrasonography ; }, }
@article {pmid11761619, year = {2001}, author = {Maliarchuk, BA and Denisova, GA and Derenko, MV and Rogaev, EI and Vlasenko, LV and Zhukova, SG}, title = {[Variability in mitochondrial DNA in Russian inhabitants from Krasnodar Krai, Belgorod and the lower Novgorod region].}, journal = {Genetika}, volume = {37}, number = {10}, pages = {1411-1416}, pmid = {11761619}, issn = {0016-6758}, mesh = {Asian Continental Ancestry Group/genetics ; DNA, Mitochondrial/*genetics ; European Continental Ancestry Group/genetics ; *Genetics, Population ; Humans ; Russia ; }, abstract = {Mitochondrial DNA (mtDNA) polymorphism was examined in three Russian populations from the European part of Russia (Krasnodar Krai, Belgorod, and Nizhnii Novgorod oblast). This analysis revealed that mitochondrial gene pool of Russians was represented by the mtDNA types belonging to groups H, V, pre-V, HV*, J, T, U, K, I, W, and X. The major groups (average frequency over 5%) were H, V, J, T, and U. Mongoloid admixture in Russians, constituting only 1%, was revealed in the form of mtDNA types of groups C and D. Analysis of the frequency distribution of the mtDNA type groups indicated the absence of genetic differences between the Russian populations studied.}, }
@article {pmid11761618, year = {2001}, author = {Derenko, MV and Denisova, GA and Maliarchuk, BA and Dambueva, IK and Luzina, FA and Lotosh, EA and Dorzhu, ChM and Karamchakova, ON and Solovenchuk, LL and Zakharov, IA}, title = {[Structure of the gene pool of ethnic groups from the Altai-Sayan region from data on mitochondrial polymorphism].}, journal = {Genetika}, volume = {37}, number = {10}, pages = {1402-1410}, pmid = {11761618}, issn = {0016-6758}, mesh = {DNA, Mitochondrial/*genetics ; *Ethnic Groups ; *Gene Pool ; Phylogeny ; *Polymorphism, Genetic ; Siberia ; }, abstract = {Using the data on mitochondrial DNA (mtDNA) polymorphism, genetic structures of the four Turkic-speaking ethnic groups of Altai-Sayan highlands, Southern Altaians (Altai-Kizhi), Khakassians, Shorians, and Sojots, were described. Mitochondrial gene pools of the populations examined were characterized by different ratios between Mongoloid (M*, C, D, E, G, A, B, and F) and Caucasoid (H, U, T, J, and K) mtDNA lineages. All the populations studied had a strongly pronounced Mongoloid component, the frequency of which was 88.2% in Sojots, 75.9% in Khakassians, 67.4% in Altaians, and 64.3% in Shorians. Maximum frequency of the Caucasoid component (35.7%) was observed in Shorians. Phylogenetic and statistical analyses of the mtDNA group frequency distribution patterns in the gene pools of the ethnic populations of Altai-Sayan highlands and the adjacent territories showed that the populations of the region fell into three groups. The first group included Khakassians, Tuvinians and Altaians, the second group consisted of Sojots, Buryats, and Mongols, while the third group was composed of Uigurs, Kazakhs, and Kyrgyzes. The isolated position of Shorians among the populations examined can be explained by their different anthropological composition and their presumptive relatedness to Finno-Ugric populations of Siberia.}, }
@article {pmid11603326, year = {2001}, author = {Denisova, L and Vorontsova, S and Safiullina, I and Emel'ianova, L}, title = {[Role of magnetic resonance imaging in the complex radiation diagnosis of hormonally active adrenal tumors].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {4}, pages = {25-34}, pmid = {11603326}, issn = {0042-4676}, mesh = {Adenocarcinoma/*diagnosis ; Adenoma/*diagnosis ; Adrenal Gland Neoplasms/*diagnosis ; Adult ; Aged ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; }, abstract = {Based on the results of examination of 30 patients with hormonally active adrenal tumors, the authors consider the MRI sympatomatology of their different types and the potentialities of the technique in the complex radiation diagnosis of this pathology. The authors present their assessments of the relative intensity of a signal and the structure of each type of hormone-producing tumors of the glands by using different MRI pulse sequences that may be useful in establishing a presumptive morphological diagnosis. They identify MRI sequences that are of the greatest informative value for the diagnosis of each type of hormonally active adrenal tumors. There is evidence for that MRI is highly effective in detecting all types of hormonally active adrenal tumors and, in the context of their topographic and anatomic diagnosis, has an unquestionable advantage over ultrasonography and X-ray computed tomography in some cases.}, }
@article {pmid11603325, year = {2001}, author = {Portnoi, L and Denisova, L and Utkina, E and Denisov, V and Safiullina, I and Emel'ianova, L}, title = {[Magnetic resonance cholangiopancreatography and a problem in diagnosis of hepatopancreatoduodenal diseases].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {4}, pages = {14-24}, pmid = {11603325}, issn = {0042-4676}, mesh = {Adult ; Aged ; Cholangiopancreatography, Endoscopic Retrograde ; Cholestasis/diagnosis ; Digestive System/anatomy & histology/diagnostic imaging ; Digestive System Diseases/*diagnosis/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; }, abstract = {Based on the findings of 54 magnetic resonance studies, the authors used 19 of them authors to study the types of normalcy. A role of the new noninvasive technique magnetic resonance cholangiopancreatography (MRCPG) in the diagnosis of hepatopancreatoduodenal diseases is assessed. The potentialities of MRCPG in the detection of most common diseases and malformations of the biliary system are demonstrated. Comparative studies of MRCPG and endoscopic retrograde cholangiopancreatography (ERCPG) were conducted in 18 cases. The paper shows a methodological approach to MRCPG and analyzes the studies by describing the MR semiotics of major diseases. Emphasis is laid on how it is important to combine routine MRI and MRCPG in certain diagnostic situations. The authors consider that MRCPG is able to replace X-ray endoscopic studies and primarily ERCPG in diagnostic terms, by reserving their therapeutical functions for itself. MRCPG has great potentialities that, require further investigations and analysis.}, }
@article {pmid11588961, year = {2001}, author = {Gnusareva, NA and Duĭsenova, RB and Karal'nik, BV and Omarov, TO and Denisova, TG}, title = {[Detection of antigen-binding lymphocytes in the diagnosis of tuberculosis].}, journal = {Problemy tuberkuleza}, volume = {}, number = {5}, pages = {41-42}, pmid = {11588961}, issn = {0032-9533}, mesh = {*Cell Migration Inhibition ; Diagnosis, Differential ; Fluoroscopy ; Humans ; Indicators and Reagents ; Lymphocytes/*immunology ; Mycobacterium tuberculosis/isolation & purification ; Pneumonia/diagnosis/immunology ; Rosette Formation ; Sensitivity and Specificity ; Time Factors ; Tuberculin/*immunology ; Tuberculosis/*diagnosis/diagnostic imaging/immunology ; Tuberculosis, Pulmonary/*diagnosis/diagnostic imaging/immunology ; }, abstract = {The efficiency of diagnosis of active tuberculosis was evaluated from detection of tuberculin-receptor lymphocytes [antigen-binding lymphocytes (ABL)] by the indirect rossette-formation test with the red blood cell reagent designed. Sixty two patients with tuberculosis (of them 10 patients with extrapulmonary tuberculosis), 10 with lobular pneumonia, and 27 healthy individuals cal were examined. Positive results of fluography, smear microscopy, bacteriological study, leukocytic migration inhibition test, and test for ABL were obtained in 84, 40, 50, 39, and 100%, respectively. The controls had negative tests. Thus, ABL detection was the method of choice in tuberculosis diagnosis.}, }
@article {pmid11507978, year = {2001}, author = {Reshetnikov, OV and Kurilovich, SA and Denisova, DV and Zavyalova, LG and Tereshonok, IN}, title = {Prevalence of dyspepsia and irritable bowel syndrome among adolescents of Novosibirsk, western Siberia.}, journal = {International journal of circumpolar health}, volume = {60}, number = {2}, pages = {253-257}, pmid = {11507978}, issn = {1239-9736}, mesh = {Adolescent ; Colonic Diseases, Functional/*epidemiology ; Dyspepsia/*epidemiology ; Female ; Humans ; Male ; Prevalence ; Siberia/epidemiology ; Surveys and Questionnaires ; }, abstract = {The study was undertaken to determine the prevalence of gastrointestinal symptoms in a community-based population of adolescents. All students in grades 9-11 of four randomly chosen schools in one of the typical districts of Novosibirsk were invited to participate. A total of 449 students participated (189 boys, 260 girls aged 14-17), all of them completed the Russian version of the Bowel Disease Questionnaire. Dyspepsia was reported more frequently by girls than boys (27% vs 16%). The prevalence of irritable bowel syndrome defined according to the Rome criteria was 24% in girls and 14% in boys. Among students with dyspepsia, 49% had sought medical advice, and 37% had undergone upper gastrointestinal endoscopy or X-ray series, for IBS the corresponding figures were 49% and 24%. School absenteeism was reported by 57% of dyspepsia sufferers, and by 62% of subjects with IBS. In conclusion, dyspepsia and IBS are common among adolescents of Novosibirsk with prevalence rates similar to those described in adults in Western Europe and the USA. These disorders are associated with significant disability and health care costs.}, }
@article {pmid11477614, year = {2001}, author = {Marga, M and Denisova, A and Sochnev, A and Pirags, V and Farid, NR}, title = {Two HLA DRB 1 alleles confer independent genetic susceptibility to Graves disease: relevance of cross-population studies.}, journal = {American journal of medical genetics}, volume = {102}, number = {2}, pages = {188-191}, pmid = {11477614}, issn = {0148-7299}, mesh = {Adolescent ; Adult ; Aged ; *Alleles ; DNA/genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/*genetics ; Graves Disease/*genetics/pathology ; HLA-DR Antigens/*genetics ; HLA-DRB1 Chains ; Humans ; Male ; Middle Aged ; Odds Ratio ; }, abstract = {Recent studies of Graves disease (GD) employing genome scanning techniques excluded the major histocompatibility complex as a contributor to disease liability. These findings contradict earlier population association studies. Our own earlier studies have also emphasized that genetic variation in human populations may give novel clues to disease liability and manifestations. To this end, we studied HLA class II alleles in 47 Latvian GD patients and 111 matched healthy controls. As expected, we found that DRB1*03 and DQA1*0501 (OR = 3.6, P = 0.029 and OR 2.35, P = 0.0373, respectively) were associated with GD. Unforeseen, DRB1*04 was found to be significantly increased in the patients compared to controls (OR 3.267, corrected P = 0.0319). The two DRB1 alleles conferred two non-overlapping and independent susceptibilities to GD, in that only three patients were positive for both alleles, and the removal of each allele in turn resulted in only the other DRB1 allele showing significant association with the disease. There was no heterogeneity between the two patient groups (DRB1*03 positive and DRB1*04 positive) in clinical characteristics or disease manifestations. The phenotype DRB1*03 and/or DRB1*04 was found in 34/47 patients compared to 27/111 controls yielding an OR of 7.395 (P corrected = 0.000019). We examined the structural basis of DRB1 susceptibility to GD in light of this and previous studies, showing that DRB1*03, 04, and 08 were positively associated with the disease, whereas DRB1*07 was negatively associated. Differences in protein sequences were noted at residues 54, 57, 59, and 66; positions 54, 57, and 66 are on the same face of the alpha helix. The canonical arginine 54 is replaced by glutamine in DRB1*07. At position 66, asparagine in DRB1*03 and tyrosine in DRB1*04 are replaced by phenylalanine in DRB1*07. Residue 59, likely involved in pocket formation in the antigen binding groove, is modified by replacement of tyrosine in DRB1*03, 08, and 04 and by leucine in DRB1*07. The predicted differences in the shape and charges of the proximal reaches of the antigen binding groove between DRB1*07, and 03, 04, and 08, could determine whether or not a peptide from an auto-antigen would be bound or not. Genetic variation among human populations may yield important clues to specific disease liability.}, }
@article {pmid11459075, year = {2001}, author = {Sofic, E and Denisova, N and Youdim, K and Vatrenjak-Velagic, V and De Filippo, C and Mehmedagic, A and Causevic, A and Cao, G and Joseph, JA and Prior, RL}, title = {Antioxidant and pro-oxidant capacity of catecholamines and related compounds. Effects of hydrogen peroxide on glutathione and sphingomyelinase activity in pheochromocytoma PC12 cells: potential relevance to age-related diseases.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {108}, number = {5}, pages = {541-557}, doi = {10.1007/s007020170055}, pmid = {11459075}, issn = {0300-9564}, mesh = {Animals ; Antioxidants/*pharmacology ; Biological Assay ; Catecholamines/*pharmacology ; Ceramides/biosynthesis ; Copper/pharmacology ; Dose-Response Relationship, Drug ; Free Radicals/metabolism ; Glutathione/*drug effects/metabolism ; Hydrogen Peroxide/*pharmacology ; Hydroxyl Radical/metabolism ; Neurodegenerative Diseases/*enzymology/physiopathology ; Oxidants/*pharmacology ; Oxidative Stress/drug effects/*physiology ; PC12 Cells/*drug effects/metabolism ; Peroxides/metabolism ; Rats ; Sphingomyelin Phosphodiesterase/*drug effects/metabolism ; Sphingomyelins/metabolism ; }, abstract = {The antioxidant and pro-oxidant capacity of catecholamines (CA) and related compounds were analyzed using the oxygen radical absorbance capacity (ORAC) assay. In the assay 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH), a peroxyl radical generator, ROO*; H2O2-Cu2+, mainly a hydroxyl radical generator, *OH; and Cu2+ a transition metal were used. The antioxidant effect of CA and its related compounds were in the order: neurotransmitters: dopamine (DA), norepinephrine (NE) > metabolites > amino acid precursors as measured by using AAPH. The antioxidant effect of CA and related compounds as measured by using AAPH were linearly correlated with concentration, while the antioxidant effect of CA in scavenging *OH produced by H2O2-Cu2+ increased proportionally to concentration at low concentration, but after reaching a maximum declined with increasing concentration. In the presence of Cu2+, CA acted as pro-oxidant. Glutathione (GSH) acted as a pro-oxidant when H2O2-Cu2+ or when Cu2+ alone was used as an oxidant and showed much higher pro-oxidant effect than DA, which could have relevance in the vulnerability of dopaminergic neurons to oxidative stress in the aging and aging related diseases. The antioxidant capacity of CA and many related compounds seems to be correlated with the numbers of hydroxyl groups and their position on the benzoic ring. The O-methylation and sulfate conjugation of the hydroxyl substitution inactivates both the antioxidant and pro-oxidant activities of CA. Our results show that oxidative stress induced by low (5 microM) or high (300 microM) doses H2O2 in pheochromocytoma PC12 cells significantly up-regulate the activity of Mg-dependent neutral sphingomyelinase (Sase), and significantly decreased GSH.}, }
@article {pmid11338849, year = {2001}, author = {Reshetnikov, OV and Kurilovich, SA and Denisova, DV and Zav'ialova, LG and Svetlova, IO and Tereshonok, IN and Krivenchuk, NA and Eremeeva, LI}, title = {[Prevalence and risk factors of the development of irritable bowel syndrome in adolescents: a population study].}, journal = {Terapevticheskii arkhiv}, volume = {73}, number = {2}, pages = {24-29}, pmid = {11338849}, issn = {0040-3660}, mesh = {Adolescent ; Age Factors ; Colonic Diseases, Functional/diagnosis/*epidemiology/etiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Risk Factors ; Sex Factors ; Siberia/epidemiology ; }, abstract = {AIM: To determine prevalence of irritable bowel syndrome (IBS) and associated factors in a community-based population of adolescents.

MATERIAL AND METHODS: 189 schoolboys and 250 schoolgirls aged 14-17 years from four randomly chosen schools of Novosibirsk participated in the study.

RESULTS: The prevalence of IBS defined according to Rome criteria was higher in girls (24 vs 14% in boys, p = 0.01). Colonic pain frequency was similar in both genders (11% in girls vs 9% in boys, p = 0.46), however disturbed defecation occurred significantly more often in girls than in boys (16 vs 7%, p = 0.003). Half of the subjects who reported IBS had also dyspeptic symptoms. Fiber-rich diet and/or laxatives to prevent constipation were used by 2% of boys and 7% of girls (p = 0.012). However, only one third of those having less than 3 stools a week thought it abnormal. IBS is associated with the age over 15-16 years, female gender, abdominal pain in childhood, appendectomy, irregular meals and smoking (in girls). No association was found with other socio-demographic factors and serological markers of some infections and invasions (H. pylori, G. lamblia, O. felineus, hepatitis viruses B and C). Of the persons with diagnosable IBS, 49% have consulted a physician about it, 21% have undergone upper endoscopy. School absenteeism was reported by 62% of the IBS sufferers.

CONCLUSION: IBS is common among adolescents (especially girls) with the prevalence rates similar to those described in adults from West Europe and USA. These disorders are associated with significant disability and health care costs.}, }
@article {pmid11305358, year = {2001}, author = {Seagal, J and Spectorman, E and Gershoni, JM and Denisova, GF}, title = {Use of human CD4 transgenic mice for studying immunogenicity of HIV-1 envelope protein gp120.}, journal = {Transgenic research}, volume = {10}, number = {2}, pages = {113-120}, pmid = {11305358}, issn = {0962-8819}, mesh = {AIDS Vaccines/immunology ; Animals ; CD4 Antigens/*genetics ; Cell Separation ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; HIV Antibodies/biosynthesis ; HIV Envelope Protein gp120/*immunology ; HIV-1/*immunology ; Humans ; Immunity, Cellular ; Lymphocytes/immunology ; Mice ; Mice, Transgenic ; Recombinant Proteins/immunology ; }, abstract = {HIV-1 envelope protein, gp120, is a major immunogenic protein of the AIDS virus. A specific feature of this protein is its interaction with the receptor protein, human CD4, an important component of the immune system. This interaction might affect the immunogenic properties of the gp 120 and modulate the immune response towards HIV. To test this hypothesis we used human CD4-transgenic mice for immunization with gp120. The dynamics of the immune response towards gp120, CD4 and other proteins was followed. The results show that the primary immune response to gp120 (two weeks) developed somewhat faster in CD4-transgenic mice versus non-transgenic mice. Both animals, however, ultimately mounted the same level of response over time. The primary immune response to gp120 when complexed with soluble CD4 before the immunization, developed similarly in both groups. The secondary immune response was earlier and markedly stronger in non-transgenic mice compared with the transgenic mice where a less efficient memory response to gp120 was observed. The ability of gp120 to directly interact with CD4+ helper lymphocytes appears to affect the humoral response towards this antigen. Moreover, these effects illustrate how viral modulation of these cells may in turn lead to potentially different states of immunological equilibrium.}, }
@article {pmid11295365, year = {2001}, author = {Denisova, NA and Cantuti-Castelvetri, I and Hassan, WN and Paulson, KE and Joseph, JA}, title = {Role of membrane lipids in regulation of vulnerability to oxidative stress in PC12 cells: implication for aging.}, journal = {Free radical biology & medicine}, volume = {30}, number = {6}, pages = {671-678}, pmid = {11295365}, issn = {0891-5849}, mesh = {Acetylcysteine/pharmacology ; Aging/*metabolism ; Animals ; Calcium/metabolism ; Cell Membrane/drug effects/metabolism ; Cholesterol/metabolism/pharmacology ; Enzyme Induction/drug effects ; Fluorescent Dyes ; Glutathione/metabolism ; Hydrogen Peroxide/administration & dosage/pharmacology ; Membrane Lipids/*metabolism ; Oxidative Stress/*physiology ; PC12 Cells ; Rats ; Reactive Oxygen Species/metabolism ; Sphingomyelin Phosphodiesterase/metabolism ; Sphingomyelins/metabolism/pharmacology ; }, abstract = {Previously, we reported that PC12 cells showed increased vulnerability to oxidative stress (OS) induced by H2O2 (as assessed by decrements in calcium recovery, i.e., the ability of cells to buffer Ca(2+) after a depolarization event) when the membrane levels of cholesterol (CHL) and sphingomyelin (SPH) were modified to approximate those seen in the neuronal membranes of old animals. The present study was designed to examine whether the enrichment of the membranes with SPH-CHL and increased cellular vulnerability to OS are mediated by neutral SPH-specific phospholipase C (N-Sase) and the intracellular antioxidant GSH. The results showed a significant up-regulation of N-Sase activity by both low (5 microM) and high (300 microM) doses of H2O2. However, under high doses of H2O2 the up-regulation of N-Sase is accompanied by a significant increase in reactive oxygen species and by a decrease in intracellular GSH. The enrichment of membranes with SPH-CHL significantly potentiated the effects of high doses of H2O2, by further reducing the intracellular GSH and further up-regulating the N-Sase activity. Furthermore, repleting intracellular GSH with 20 mM N-acetylcysteine treatment was sufficient to attenuate the effect of a low dose of H2O2 on Ca(2+) recovery in SPH-CHL-treated cells. Thus, these results suggested that age-related alterations in the membrane SPH-CHL levels could be important determinants of the susceptibility of neuronal cells to OS.}, }
@article {pmid11251382, year = {2000}, author = {Manam, S and Ledwith, BJ and Barnum, AB and Troilo, PJ and Pauley, CJ and Harper, LB and Griffiths, TG and Niu, Z and Denisova, L and Follmer, TT and Pacchione, SJ and Wang, Z and Beare, CM and Bagdon, WJ and Nichols, WW}, title = {Plasmid DNA vaccines: tissue distribution and effects of DNA sequence, adjuvants and delivery method on integration into host DNA.}, journal = {Intervirology}, volume = {43}, number = {4-6}, pages = {273-281}, doi = {10.1159/000053994}, pmid = {11251382}, issn = {0300-5526}, mesh = {Adjuvants, Immunologic/pharmacology ; Aluminum Compounds/pharmacology ; Animals ; Base Sequence ; DNA/analysis ; Gonads/chemistry ; Guinea Pigs ; Humans ; Mice ; Muscles/chemistry ; Oncogene Proteins, Viral/genetics ; Papillomavirus E7 Proteins ; Phosphates/pharmacology ; Plasmids/adverse effects/*genetics/*metabolism ; Skin/chemistry ; Tissue Distribution ; Vaccination ; Vaccines, DNA/*administration & dosage/*genetics ; Viral Vaccines/administration & dosage/*genetics ; Virus Diseases/prevention & control ; }, abstract = {A variety of factors could affect the frequency of integration of plasmid DNA vaccines into host cellular DNA, including DNA sequences within the plasmid, the expressed gene product (antigen), the formulation, delivery method, route of administration, and the type of cells exposed to the plasmid. In this report, we examined the tissue distribution and potential integration of plasmid DNA vaccines following intramuscular administration in mice and guinea pigs. We compared needle versus Biojector (needleless jet) delivery, examined the effect of aluminum phosphate adjuvants, compared the results of different plasmid DNA vaccines, and tested a gene (the human papilloma virus E7 gene) whose protein product is known to increase integration frequency in vitro. Six weeks following intramuscular injection, the vast majority of the plasmid was detected in the muscle and skin near the injection site; lower levels of plasmid were also detected in the draining lymph nodes. At early time points (1-7 days) after injection, a low level of systemic exposure could be detected. Occasionally, plasmid was detected in gonads, but it dissipated rapidly and was extrachromosomal - indicating a low risk of germline transmission. Aluminum phosphate adjuvant had no effect on the tissue distribution and did not result in a detectable increase in integration frequency. Biojector delivery, compared with needle injection, greatly increased the uptake of plasmid (particularly in skin at the injection site), but did not result in a detectable increase in integration frequency. Finally, injection of a plasmid DNA vaccine containing the human papilloma virus type 16 E7 gene, known to increase integration in vitro, did not result in detectable integration in mice. These results suggest that the risk of integration following intramuscular injection of plasmid DNA is low under a variety of experimental conditions.}, }
@article {pmid11245685, year = {2001}, author = {Belousov, AB and O'Hara, BF and Denisova, JV}, title = {Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus in vitro in the absence of glutamate excitation.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {21}, number = {6}, pages = {2015-2027}, pmid = {11245685}, issn = {1529-2401}, support = {DA00187/DA/NIDA NIH HHS/United States ; }, mesh = {Acetylcholine/*metabolism ; Animals ; Calcium/metabolism ; Calcium Signaling/drug effects ; Cells, Cultured ; Cerebellum/cytology/drug effects/metabolism ; Cerebral Cortex/cytology/drug effects/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Postsynaptic Potentials/drug effects/physiology ; Fluorescent Dyes ; GABA Antagonists/pharmacology ; Glutamic Acid/metabolism ; Hypothalamus/cytology/drug effects/*metabolism ; Membrane Potentials/drug effects/physiology ; Neurotransmitter Agents/*metabolism ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, Glutamate/metabolism ; Synaptic Transmission/drug effects ; Up-Regulation/drug effects ; }, abstract = {Glutamate and GABA are two major fast neurotransmitters (excitatory and inhibitory, respectively) in the CNS, including the hypothalamus. They play a key role in the control of excitation/inhibition balance and determine the activity and excitability of neurons in many neuronal circuits. Using neuronal cultures, whole-cell recording, Ca(2+) imaging, and Northern blots, we studied the compensatory regulation of neuronal activity during a prolonged decrease in glutamate excitation. We report here that after a chronic (6-17 d) blockade of ionotropic glutamate receptors, neurons in hypothalamic cultures revealed excitatory electrical and Ca(2+) synaptic activity, which was not elicited in the control cultures that were not subjected to glutamate blockade. This activity was suppressed with acetylcholine (ACh) receptor antagonists and was potentiated by eserine, an inhibitor of acetylcholinesterase, suggesting its cholinergic nature. The upregulation of ACh receptors and the contribution of ACh to the control of the excitation/inhibition balance in cultures after a prolonged decrease in glutamate activity were also demonstrated. Enhanced ACh transmission was also found in chronically blocked cerebellar but not cortical cultures, suggesting the region-specific character of glutamate-ACh interactions in the brain. We believe that in the absence of glutamate excitation in the hypothalamus in vitro, ACh, a neurotransmitter normally exhibiting only weak activity in the hypothalamus, becomes the major excitatory neurotransmitter and supports the excitation/inhibition balance. The increase in excitatory ACh transmission during a decrease in glutamate excitation may represent a novel form of neuronal plasticity that regulates activity and excitability of neurons during the glutamate/GABA imbalance.}, }
@article {pmid11201820, year = {2000}, author = {Denisova, TP and Malinov, IA}, title = {[Dynamics of changes in levels of insulin, glucagon, and C-peptide during glucose tolerance test in patients with coronary atherosclerosis].}, journal = {Terapevticheskii arkhiv}, volume = {72}, number = {12}, pages = {14-16}, pmid = {11201820}, issn = {0040-3660}, mesh = {C-Peptide/*blood ; Coronary Artery Disease/*blood/genetics ; Glucagon/*blood ; Glucose Tolerance Test ; Humans ; Insulin/*blood ; Myocardial Infarction/blood ; }, abstract = {AIM: To study velocity characteristics of changes in the levels of insulin, glucagon and C-peptide in the course of the intravenous glucose tolerance test (IGTT).

MATERIAL AND METHODS: Glucose, insulin, glucagon and peptide levels were measured in the course of IGTT performed in 50 patients with coronary atherosclerosis (CA) who survived transmural myocardial infarction, 32 individuals with hereditary predisposition to CA and 30 controls free of cardiovascular or endocrine pathology. The results were approximated using high-degree polynomes allowing calculation of the first and second derivatives (the velocity and rate of its change).

RESULTS: CA patients showed inhibited changes of blood glucose, immunoreactive insulin. The reduction of the latter lasted longer than that in the control group.

METHODS: DNA from 119 JRA patients (72 pauciarticular, 47 polyarticular) and 111 healthy controls from Latvia was genotyped for a functional repeat polymorphism in the promoter of NRAMP1 and a linked (<150 kb) microsatellite D2S1471. The findings were compared with those from HLA-DQ alleles typed previously. Chi-square analyses were performed using the Mantel-Haenszel test and stratification according to pure Latvian or pure Russian descent. Haplotype analysis was performed using the Associate program to implement the expectation-maximization algorithm based on the gene-counting technique.

RESULTS: Allele 3 at NRAMP1 conferred increased risk (odds ratios [ORs] 2.26, 2.31, and 2.19; P = 0.0006, 0.003, and 0.019) of disease in the JRA, pauciarticular, and polyarticular patient groups, respectively. Allele 2 conferred protection (OR 0.44, 0.43, and 0.46). Alleles at D2S1471 that conferred susceptibility (6 and 12) or protection (11) did so only when on a haplotype with alleles 3 or 2, respectively, at NRAMP1. Allele 3 at NRAMP1 was additive with HLA-DQ7 for susceptibility (OR 3.71, 3.71, and 4.02), and allele 2 at NRAMP1 was additive with HLA-DQ5 for protection (OR 0.19, 0.08, and 0.12).

CONCLUSION: The NRAMP1 allele conferring susceptibility to JRA drives high levels of NRAMP1 expression, while the allele associated with protection drives low levels. These 2 alleles are inversely associated with susceptibility to infectious disease, consistent with their maintenance in populations through balancing selection.}, }
@article {pmid10852036, year = {1999}, author = {Denisova, LIa and Baturina, II and Zakabunin, AI and Afinogenova, GN and Pustoshilova, NM}, title = {[The determination of lipopolysaccharide admixtures in protein preparations].}, journal = {Zhurnal mikrobiologii, epidemiologii, i immunobiologii}, volume = {}, number = {5}, pages = {109-112}, pmid = {10852036}, issn = {0372-9311}, mesh = {Biotinylation ; Calibration ; Collodion ; *Drug Contamination ; *Escherichia coli ; Indicators and Reagents ; Lipopolysaccharides/*analysis ; Membranes, Artificial ; Periodic Acid ; Recombinant Proteins/*analysis ; Solutions ; }, abstract = {A new method for the determination of lipopolysaccharide (LPS) admixtures in protein solutions has been developed. The method includes the periodate oxidation of LPS, biotinylation with biotin hydraside, immobilization on a nitrocellulose membrane and the development of biotinylated LPS in the streptavidin--alkaline phosphatase system. Proteins are previously removed from the solution by treatment with hot phenol. Development with the use of 5-bromoinodyl phosphate and nitrotetrazolium blue makes it possible to detect about 30 pg of LPS immobilized on the nitrocellulose membrane.}, }
@article {pmid10832397, year = {2000}, author = {Portnoĭ, LM and Denisova, LB and Stashuk, GA and Nefedova, VO}, title = {[Magnetic resonance imaging in the diagnosis of gastric cancer: X-ray versus MRI anatomic findings].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {1}, pages = {26-40}, pmid = {10832397}, issn = {0042-4676}, mesh = {Administration, Oral ; Adult ; Aged ; Barium Sulfate/administration & dosage ; Carcinoma/*diagnosis ; Contrast Media/administration & dosage ; Diagnosis, Differential ; Diagnostic Errors ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiography ; Sensitivity and Specificity ; Stomach/*diagnostic imaging/*pathology ; Stomach Neoplasms/*diagnosis ; }, abstract = {The paper assesses the present-day role of MRI in the diagnosis of gastric cancer. The authors consider the major prerequisites for the main aim of their study to be: 1) a dramatic incidence of diffuse (endophytic) gastric carcinoma, which requires significant correction of today's approaches to its diagnosis and 2) a rather biased and, in the authors' opinion, present-day mainly negative attitude towards MRI of the stomach as a diagnostic method for its tumor lesions. By applying the X-ray-MRI anatomic principle to the comparative study of MRI findings in 50 patients with predominantly gastric intramural carcinoma and in 25 patients without gastric tumors (controls), the authors present their methods for gastric MRI, the MRI semiotics of gastric cancer by concurrently touching upon a variety of problems that characterize the potentialities of MRI of the stomach in the diagnosis of its tumor lesions, including their differential diagnosis. As a result, the authors highly appreciate gastric MRI and consider this method to be included into the diagnostic algorithm of radiation techniques used in the diagnosis of gastric cancer, which should occupy its definite diagnostic place.}, }
@article {pmid10802890, year = {2000}, author = {Kharitonchik, LA and Kodentsova, VM and Vrzhesinskaia, OA and Denisova, SN and Spirichev, VB}, title = {[Vitamin B 6 metabolism in phenylketonuria].}, journal = {Voprosy meditsinskoi khimii}, volume = {46}, number = {1}, pages = {81-88}, pmid = {10802890}, issn = {0042-8809}, mesh = {Child ; Female ; Humans ; Male ; Phenylketonurias/*metabolism ; Pyridoxal Phosphate/blood ; Pyridoxic Acid/urine ; Pyridoxine/*metabolism ; Riboflavin/metabolism ; }, abstract = {Based on the analysis of the dependence of 4-pyridoxic acid urinary excretion from pyridoxal-5'-phosphate blood plasma level and its statistic distribution it has been shown that vitamin B-6 metabolism in children suffering from phenylketonuria and therefore the criteria of the body saturation with this vitamin differ from those for healthy people. Increased pyridoxal-5'-phosphate blood plasma level has been demonstrated for PKU children. The concentration of 11 ng/ml should be considered as a bottom border of the adequate supply with vitamin B-6. The elevated vitamin B-2 intake approximates vitamin B-6 status indexes of sick children to those usually measured in healthy children. The necessity for the reevaluation of vitamin B-2 and B-6 optimal diet content under this disease and its biochemical validation are discussed.}, }
@article {pmid10781835, year = {2000}, author = {Denisova, GF and Zerwanitzer, M and Denisov, DA and Spectorman, E and Mondor, I and Sattentau, Q and Gershoni, JM}, title = {Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response.}, journal = {Molecular immunology}, volume = {37}, number = {1-2}, pages = {53-58}, pmid = {10781835}, issn = {0161-5890}, mesh = {Amino Acid Sequence ; Animals ; Antibodies, Anti-Idiotypic/*immunology ; *Antibody Formation ; Cross Reactions ; Epitopes/*immunology ; HIV Envelope Protein gp120/immunology ; HIV-1/immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; }, abstract = {The primary humoral response produces antigen-specific antibodies so to clear the initial infection, and generates a population of corresponding memory cells to prevent infection by future encounters with the same pathogen. The continuous genetic modification of a pathogen's exterior, however, is one mechanism used to evade the immune defenses of its host. Here we describe a novel means, involving anti-idiotypic antibodies, by which the host can counteract such pathogen genetic alterations by modulation of its primary humoral response. An autoimmune response against primary antibodies, Ab1's, creates anti-idiotypic antibodies (Ab2's), some of which (designated Ab2alpha) are able to bind the Ab1/antigen complex. We have discovered that binding of Ab2alpha to its corresponding Ab1 can expand Ab1's ability to bind variations of its antigen. This expanded epitope cross-reactivity is shown not only to increase the binding activity of Ab1 but also its ability to neutralize a variant infectious virus. MAb M77 is an Ab1, which is highly strain-specific for the HIV-1 envelope protein gp120(IIIB). This Ab1 can be rendered cross-reactive and neutralizing for an otherwise resistant HIV strain by its interaction with a unique anti-idiotypic Ab2alpha (GV12). Furthermore, molecular characterization of this expanded cross-reactivity was accomplished using combinatorial phage display peptide libraries.}, }
@article {pmid10769463, year = {2000}, author = {Mel'nikova, EV and Shchekina, OG and Borisova, MN and Denisova, LB and Baranova, IN}, title = {[Characteristics of the strategy of intensive care of unconscious children].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {1}, pages = {36-38}, pmid = {10769463}, issn = {0201-7563}, mesh = {Adolescent ; Age Factors ; Central Nervous System Diseases/therapy ; Child ; Child, Preschool ; *Critical Care/methods ; Humans ; Infant ; Infant, Newborn ; Intensive Care, Neonatal/methods ; Meningitis, Bacterial/therapy ; Meningoencephalitis/therapy ; Unconsciousness ; }, abstract = {Three major groups can be distinguished among children hospitalized in resuscitation and intensive care wards in a state of unconsciousness: patients with bacterial meningitis and meningoencephalitis, viral meningoencephalitis, and noninfectious involvement of the NCS. Common strategy of treatment of these patients is characterized by some specific features: etiotropic antibiotic therapy in group 1 patients, antiviral drugs in group 2, and mainly symptomatic measures in group 3. Immunotherapy used in each of these groups is substitute in group 1, immunomodulating and immunostimulating in group 2 and even more so in group 3. Better results in group 1 are due to highly effective etiotropic antibiotics and drugs.}, }
@article {pmid10717927, year = {2000}, author = {Denisova, GA and Oshchepkova, EV and Balakhonova, TV and Kheĭmets, GI and Arabidze, GG}, title = {[Blood flow in affected major arteries of head in hypertensive patients].}, journal = {Terapevticheskii arkhiv}, volume = {72}, number = {2}, pages = {49-52}, pmid = {10717927}, issn = {0040-3660}, mesh = {Adult ; Aged ; Arteriosclerosis/complications/diagnostic imaging/*physiopathology ; Blood Flow Velocity ; Brain/*blood supply ; Carotid Artery, Internal/diagnostic imaging/*physiopathology ; Female ; Humans ; Hypertension/complications/diagnostic imaging/*physiopathology ; Male ; Middle Aged ; Severity of Illness Index ; Ultrasonography, Doppler, Duplex ; Vertebral Artery/diagnostic imaging/*physiopathology ; }, abstract = {AIM: To assess blood flow in intracranial internal carotid and vertebral arteries in patients with essential hypertension (EH) and hemodynamically insignificant atherosclerotic lesions and deformities of major arteries of the head (MAH).

MATERIALS AND METHODS: The blood flow was assessed in 55 untreated patients (mean age 53 +/- 1 years) with mild, moderate or severe hypertension. 20 healthy patients served control. Duplex scanning was performed using ACUSON unit.